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Cristae In the 1950s, seminal electron microscopy studies led shape of mitochondria, fusion and fission are crucial
Invaginations of the to the canonical view of mitochondria as bean-shaped for maintaining the functional properties of the mito-
mitochondrial inner organelles. These studies revealed the ultrastructural chondrial population, including its respiratory capacity.
membrane.
hallmarks of mitochondria, which include double lipid Moreover, mitochondrial dynamics has key roles in
Nebenkern structure
membranes and unusual inner membrane folds termed mammalian development, several neurodegenerative
A cytosolic structure, found in cristae . Recent studies have led to renewed appre- diseases and apoptosis.
some insect spermatids, that is ciation for the fact that the mitochondrial structure
formed by the fusion of is highly dynamic1,2. Mitochondria have drastically Mitochondria as dynamic organelles
mitochondria.
different morphologies depending on the cell type By several criteria, mitochondria are dynamic
and, even in the same cell, mitochondria can take organelles. First, the shape and size of mitochondria
on a range of morphologies, from small spheres or are highly variable and are controlled by fusion and
short rods to long tubules. In fibroblasts, for example, fission. Second, mitochondria are actively transported
mitochondria visualized with fluorescent proteins or in cells and they can have defined subcellular distribu-
specific dyes typically form tubules with diameters of tions. Finally, the internal structure of mitochondria
~0.5 mm, but their lengths can range from 1–10 mm can change in response to their physiological state.
or more.
Even more remarkably, imaging studies in live Dynamic shape. The length, shape, size and number
cells indicate that mitochondria constantly move and of mitochondria are controlled by fusion and fission
undergo structural transitions. Mitochondrial tubules (FIG. 1a). At steady state, the frequencies of fusion and
move with their long axes aligned along cytoskeletal fission events are balanced 4 to maintain the overall
tracks3. Individual mitochondria can encounter each morphology of the mitochondrial population. When
other during these movements and undergo fusion, this balance is experimentally perturbed, dramatic
resulting in the merging of the double membranes and transitions in mitochondrial shape can occur. Genetic
the mixing of both lipid membranes and intramito- studies in yeast and mammals indicate that cells with
chondrial content (BOX 1). Conversely, an individual a high fusion-to-fission ratio have few mitochondria,
mitochondrion can divide by fission to yield two or and that these mitochondria are long and highly inter-
more shorter mitochondria. connected5–8 (FIG. 2). Conversely, cells with a low fusion-
What are the molecular mechanisms that underlie to-fission ratio have numerous mitochondria that are
Division of Biology,
California Institute of these unusual behaviours, and do they have conse- small spheres or short rods — these are often referred
Technology, Pasadena, quences for mitochondrial function and cell physio to as ‘fragmented mitochondria’. In vivo, such changes
California 91125, USA. logy? In this Review, we discuss the dynamic nature in dynamics control mitochondrial morphology dur-
Correspondence to D.C.C. of mitochondria and summarize the mechanisms that ing development. For example, during Drosophila
e-mail: dchan@caltech.edu
doi:10.1038/nrm2275
drive mitochondrial fusion and fission. In addition, we melanogaster spermatogenesis, many mitochondria
Published online discuss recent insights into how these processes affect synchronously fuse to form the Nebenkern structure,
10 October 2007 the function of mitochondria. As well as controlling the which is required for sperm motility9.
Box 1 | What happens to mitochondrial components after fusion? lines of evidence from neuronal studies suggest that mito-
chondrial transport is regulated. First, mitochondria are
recruited to regions with high energy demands, including
active growth cones, presynaptic sites and postsynaptic
+ Wild type
sites13,16,17. Such recruitment is regulated by neuronal acti-
vation, further arguing that the recruitment of mitochon-
dria is responsive to the local metabolic state. Second,
neuronal mitochondria pause most often at sites that lack
other mitochondria, resulting in a well-spaced axonal
mitochondrial distribution14. Third, studies with the
membrane-potential indicator dye JC‑1 suggest that mito-
+ Fusion mutant
chondria with high membrane potential preferentially
migrate in the anterograde direction, whereas mitochon-
dria with low membrane potential move in the retrograde
direction14. These migration patterns suggest that active
In time-lapse movies of labelled mitochondria in living cells, mitochondria are observed
to undergo cycles of fusion and fission. With each fusion event, two mitochondria are
mitochondria are recruited to distal regions with high
Nature Reviews | Molecular Cell Biology energy requirements, whereas impaired mitochondria
merged into one. Intuitively, true fusion would be expected to involve outer membrane
and inner membrane fusion, which would also result in mixing of the matrix contents. are returned to the cell soma, perhaps for destruction
Indeed, these expectations have been experimentally confirmed. Apparent fusion events or repair. Finally, mitochondrial transport along axons
that have been visualized in cells can be confirmed by a cell-hybrid mitochondrial fusion responds to local concentrations of nerve growth factor
assay6,32 (see figure). In this assay, mitochondria in two distinct cell lines are differentially (NGF), suggesting that specific signalling pathways
labelled with mitochondrially targeted green fluorescent protein (GFP) and DsRed. control mitochondrial recruitment and retention16,18.
The cell lines are co-plated onto cover slips and exposed briefly to polyethylene glycol,
a chemical that induces adjacent cells to fuse into cell hybrids. After a recovery period, Dynamic internal structure. In addition to changes in
the cell hybrids are examined for mitochondrial fusion. In cell hybrids from normal cells,
the overall shape of mitochondria, the internal structures
mitochondrial fusion results in mitochondria that carry both GFP and DsRed (see figure,
top). Cells that are defective for mitochondrial fusion form cell hybrids with distinct red
of mitochondria are also dynamic. Three-dimensional
and green mitochondria (see figure, bottom). A conceptually similar assay can be tomography of cryopreserved samples has provided new
performed with yeast cells by allowing labelled yeast strains to mate and form zygotes4. views of inner membrane organization and plasticity19.
By using matrix-targeted fluorophores, these assays show that mitochondrial fusion The inner membrane can be divided into distinct regions:
results in mixing of the matrix contents. Moreover, by using mitochondrial markers that the inner boundary membrane, the cristae membrane
are localized to the outer or inner membranes, fusion of the individual membranes can and the cristae junctions (FIG. 1c). The inner boundary
be experimentally demonstrated; under normal conditions, outer and inner membrane membrane comprises the regions in which the inner
fusion appear to be closely synchronized. membrane is in close proximity to the outer membrane.
An important question is what happens to mitochondrial DNA (mtDNA) after fusion. These regions are probably important for protein import
Each mitochondrion contains multiple copies of the mtDNA genome that are organized
and might be the sites of coupled outer and inner mem-
into one or more nucleoids. After fusion, these nucleoids appear to be motile and can
potentially interact with each other73. In mammalian cells, mtDNA recombination has
brane fusion. The cristae junctions are narrow ‘neck’
been documented, but its extent and importance is unclear. regions that separate the inner boundary membrane
from the involuted cristae membrane. Cytochrome c, an
intermembrane-space protein, is enriched in the space
Dynamic subcellular distribution. Mitochondrial trans- that is encased by cristae membranes, and the regulated
port is required to distribute mitochondria throughout opening of cristae junctions might be important for its
the cell (FIG. 1b). In most cells, mitochondria are highly relocalization during apoptosis20.
motile and travel along cytoskeletal tracks. Mitochondrial These regions of the mitochondrial inner membrane
transport depends on the actin cytoskeleton in budding are not only morphologically distinct but also appear to
yeast10 and on both actin and microtubules in mam- constitute separate functional domains. Proteins that
malian cells3,11,12. Depending on the cellular context, are involved in the translocation of proteins through
these transport processes can ensure proper inheritance the inner membrane, such as the TIM23 complex, are
of mitochondria or can recruit mitochondria to active enriched in the inner boundary membrane, whereas
regions of the cell. For example, in budding yeast, proteins that are involved in oxidative phosphorylation
Anterograde
mitochondria are transported into and retained in the are enriched in the cristae membranes21–23. In addition,
The direction from the cell developing bud to ensure mitochondrial inheritance to the structure of mitochondrial membranes is linked to the
body towards the periphery. the daughter cell10. metabolic state of mitochondria (FIG. 1c). Purified mito-
This regulation of mitochondrial distribution is par- chondria placed in low ADP conditions have limited
Retrograde
ticularly evident in neurons. Quantitative measurements respiration and have an ‘orthodox’ morphology, charac-
The direction from peripheral
regions towards the cell body. of neuronal mitochondrial transport have reported rates terized by narrow cristae and few cristae junctions per
ranging from 0.4 µm min–1 (Ref. 13) to 0.1–1 µm sec–1 cristae compartment. Under high ADP and substrate
Oxidative phosphorylation (refs 11,14,15). Such directed movements are not continu- conditions, isolated mitochondria have high respiratory
A biochemical pathway for ATP ous; rather, they are saltatory, with pauses often followed activity and a ‘condensed’ morphology, characterized
production that results in
oxygen consumption and is
by a reversal of direction. These patterns might reflect by larger cristae and several cristae junctions per cristae
localized to the mitochondrial the attachment and detachment of cytoskeletal motors. compartment19. It is unknown how inner membranes
cristae. Although these movements can appear chaotic, several convert between these states, but inner membrane fusion
Low [ADP]
during fusion29.
Mgm1 is a dynamin-related protein that is essential
for fusion of the mitochondrial inner membranes in
High [ADP] yeast30, a function that is consistent with its localization
to the intermembrane space and its association with the
inner membrane. The mammalian orthologue OPA1
is also essential for mitochondrial fusion28,31. In yeast,
Figure 1 | Mitochondria as dynamic organelles. a | Mitochondrial fusion and fission the outer membrane protein Ugo1 physically links Fzo1
control mitochondrial number and size. With fusion, Nature
two mitochondria becomeCell
a single and Mgm1, but no mammalian orthologue has yet been
Reviews | Molecular Biology
larger mitochondrion with continuous outer and inner membranes. Conversely, a single discovered2.
mitochondrion can divide into two distinct mitochondria by fission. b | In mammalian The membrane potential across the mitochondrial
systems, mitochondria are distributed throughout the cytoplasm by active transport along inner membrane is maintained by the electron trans-
microtubules and actin filaments. Distinct molecular motors transport the mitochondria in port chain and is essential for mitochondrial fusion26,32.
anterograde or retrograde directions. c | Inner membrane dynamics. The diagram Ionophores that dissipate the mitochondrial membrane
indicates the different regions of the inner membrane. The bottom panels show electron
potential cause mitochondrial fragmentation, owing to
microscopy (EM) tomograms of two mitochondria under different metabolic conditions
(red, outer membrane; yellow, inner boundary membrane; green, cristae membrane). an inhibition of mitochondrial fusion32,33. In an in vitro
Cristae organization can vary widely, often in response to the bioenergetic state of the fusion assay, both the proton and the electrical gradient
cell: an ‘orthodox’ cristae morphology, with narrow cristae and few cristae junctions per components of the membrane potential are important26.
cristae compartment, is found in low ADP conditions, whereas a ‘condensed’ morphology, The mechanistic link between membrane potential and
with larger cristae and several junctions per cristae compartment, is found in high fusion remains to be resolved, but one factor appears to
ADP conditions19. EM images reproduced with permission from Ref. 19 (2006) Elsevier. be the dependence of post-translational processing of
CJ, cristae junction; CM, cristae membrane; IBM, inner boundary membrane; IM, inner OPA1 on the membrane potential34.
membrane; IMS, intermembrane space; OM, outer membrane. Recent work has also identified mitochondrial lipids
as important factors in fusion. Mitochondrial morphol-
ogy screens in yeast identified members of the ergosterol
and fission might be involved19. Taken together, these synthesis pathway as being required for normal mito-
observations indicate that inner membrane morphology chondrial morphology35,36. Recently, mitochondrial
is intimately related to bioenergetics, although the causal phospholipase D has been identified as a protein that is
Coiled coil
relationship remains unclear. important for mitochondrial fusion37. This mitochon-
A structural motif that is
formed by polypeptide drial outer membrane enzyme hydrolyses cardiolipin to
sequences that contain Mediators of fusion and fission generate phosphatidic acid. Interestingly, ergosterol has
hydrophobic heptad repeats. Molecular analysis of mitochondrial morphology began been associated with yeast vacuole fusion38, and phos-
with the discovery in 1997 of the D. melanogaster fusion phatidic acid is thought to play a part in generating the
Dynamin
A large GTPase that is thought
factor fuzzy onions (FZO), a mitochondrial outer mem- membrane curvature that is required for SNARE-mediated
to mediate vesicle scission brane GTPase that is required for the fusion of mito- fusion39. Thus, specific lipids might have similar roles in
during endocytosis. chondria during spermatogenesis9. FZO is the founding distinct types of membrane fusion.
No fusion Wild type No fission This modification of DRP1 might affect its association
Mfn-null DRP1 K38A with mitochondrial membranes. Mitochondrial fission is
also regulated by the cell cycle. For example, mitochondria
in HeLa cells are usually tubular, but they become more
fragmented during mitosis, a phenomenon that might
facilitate the partitioning of mitochondria to daughter
cells during cytokinesis. This regulated fragmentation of
mitochondria is due to increased mitochondrial fission,
and phosphorylation of DRP1 during mitosis has been
implicated55.
Figure 2 | Mitochondrial fusion and fission regulate morphology. Mitochondrial In addition to the genes that encode core fusion and
length, size and connectivity are determined by theNature
relativeReviews
rates of| Molecular Cell Biology
mitochondrial fusion fission components, other genes can affect mitochon-
and fission. In wild-type cells (shown in the central panel), mitochondria form tubules of drial morphology. Large-scale visual screens for aberrant
variable length. In the absence of mitochondrial fusion (for example, in mitofusin (Mfn)-
mitochondrial morphology in mutant yeast have yielded
null cells (shown in the left panel), which lack MFN1 and MFN2), unopposed fission results
in a population of mitochondria that are all fragmented. Conversely, decreased fission
numerous genes of interest and provided general insights
relative to fusion (for example, in DRP1 K38A cells (shown in the right panel), which have into the control of mitochondrial morphology35,36. These
a dominant-negative form of dynamin-related protein-1 (DRP1)) results in elongated and screens suggest that several cellular pathways influence
highly interconnected mitochondria. Scale bar represents 10 µm. mitochondrial morphology and inheritance, including
ergosterol biosynthesis, mitochondrial protein import,
actin dynamics, vesicular fusion and ubiquitin-mediated
Mitochondrial membrane Mitochondrial fission. Mitochondrial fission requires protein degradation. The close interplay between mito-
potential the recruitment of a dynamin-related protein (Dnm1 in chondrial protein import and morphology has been
The electrochemical gradient yeast and DRP1 in mammals) from the cytosol (FIG. 4). emphasized by the recent finding that the mitochondrial
that exists across the Both Dnm1 and DRP1 assemble into punctate spots on morphology genes MMM1, MDM10 and MDM12 have a
mitochondrial inner
membrane.
mitochondrial tubules, and a subset of these complexes direct role in the assembly of β‑barrel proteins in the outer
lead to productive fission events5,7,8. By analogy with the mitochondrial membrane56.
Ergosterol classical function of dynamin in endocytosis, Dnm1
A steroid compound that is a and DRP1 are thought to assemble into rings and spirals Proteins that are required for mitochondrial transport.
component of yeast cell that encircle and constrict the mitochondrial tubule Energy-dependent molecular motors transport mitochon-
membranes and which might
have a role similar to that of
during fission25. Consistent with this model, purified dria along cytoskeletal filaments. Along microtubules,
cholesterol in mammalian cell Dnm1 can indeed form helical rings and spirals in vitro, multiple kinesin family members and cytoplasmic dynein
membranes. with dimensions that are similar to those of constricted have been implicated in anterograde and retrograde
mitochondria40. Moreover, Dnm1 assembly is required mitochondrial transport, respectively3. Recent work has
SNARE for fission activity41. clarified the linkage between mitochondria and kinesin‑1.
(soluble N‑ethylmaleimide-
sensitive fusion protein (NSF)
The recruitment of Dnm1 to yeast mitochondrial fis- Genetic screens in D. melanogaster identified milton
attachment protein (SNAP) sion sites involves three other components. One of these and Miro, both of which are required for anterograde
receptor). A highly α‑helical is Fis1, a mitochondrial integral outer membrane protein mitochondrial transport in neurons57,58. Milton interacts
protein that mediates the that is essential for fission42–44. Fis1 binds indirectly to directly with kinesin and Miro, which is a mitochondrial
specific fusion of vesicles with
Dnm1 through one of two molecular adaptors, Mdv1 outer membrane protein that has GTPase and Ca2+-bind-
target membranes.
or Caf4 (Ref. 45) (FIG. 4b). Either Mdv1 or Caf4 is suffi- ing EF‑hand domains59. In yeast, disruption of the Miro
F-box protein cient to allow the Fis1-dependent recruitment of Dnm1, orthologue Gem1 results in abnormalities in mitochon-
A protein containing an F-box although Mdv1 has a more important role in mediating drial morphology and poor respiratory activity60. Both
motif, a small domain that is fission. FIS1, the mammalian homologue of Fis1, is also GTP-binding and Ca2+-binding motifs are essential for
used for protein interactions.
essential for mitochondrial fission46, but no homologues Gem1 function, which appears not to be involved in
The best-characterized F-box
proteins are components of an of Mdv1 or Caf4 are currently known. FIS1 and DRP1 fusion or fission. Depending on the cell type, mitochon-
E3 ubiquitin ligase, and help in are also required for the fission of peroxisomes47,48. dria can also travel along actin filaments under the control
ubiquitin-dependent protein of myosin motors3.
degradation by recognizing Other regulators of dynamics
specific substrates.
Mitochondrial fusion and fission activities are probably Proteins that mediate inner membrane morphology.
β-barrel protein coordinated with cellular physiology. In yeast, the steady- Studies of mitochondrial inner membrane structure are
A protein composed of a state levels of Fzo1 are controlled by the F‑box protein complicated by the intimate link between mitochondrial
β-sheet that is rolled up Mdm30, which negatively regulates Fzo1 levels in a bioenergetics and cristae structure. As a result, disruption
into a cylinder. One such proteasome-independent manner49,50. In mammalian of the proteins that are important for bioenergetics can
mitochondrial β-barrel protein
is VDAC (voltage-dependent
cells, post-translational modification of DRP1 regulates its lead to a secondary effect on inner membrane structure.
anion channel), which forms a function in mitochondrial fission. The mitochondrial E3 Nevertheless, several proteins probably have a specific
pore in the outer membrane. ubiquitin ligase MARCH5 is essential for mitochondrial role in controlling cristae structure. In addition to their
fission51. This requirement is probably related to the abil- roles in mitochondrial fusion, Mgm1 and OPA1 are
Kinesin ity of MARCH5 to promote DRP1 ubiquitylation and to important for cristae structure. Loss of Mgm1 in yeast
A microtubule-based molecular
motor protein that is most
associate physically with ubiquitylated DRP1 (Refs 52,53). or knockdown of OPA1 in mammalian cells results in
often directed towards the plus Furthermore, during apoptosis, sumoylation of DRP1 is disorganized inner membrane structures30,61–64. In both
end of microtubules. activated in a BAX- and/or BAK-dependent manner54. cases, homo-oligomeric interactions are involved30,64.
a Wild-type cells b Fusion-deficient cells can occur in the absence of mitochondrial fission. An
important issue to resolve in future studies is how fission
is related to the permeabilization of mitochondria.
Surprisingly, the apoptotic proteins BAX and BAK,
Fusion which have well-established pro-apoptotic roles in
mitochondrial membrane permeabilization, also appear
to regulate mitochondrial morphology. BAX and BAK
Defective double-knockout cells have fragmented mitochondria
mitochondrion due to reduced mitochondrial fusion87, although the
extent of this effect depends on the experimental sys-
tem88. Little is known about how BAX and BAK mediate
their effects on mitochondrial morphology, but BAX
influences MFN2 distribution on the mitochondrial
outer membrane87 and BAK associates with MFN1 and
Fission MFN2 (Ref. 88).
In conjunction with MOMP, remodelling of the cristae
membranes is required for the rapid and efficient release
of cytochrome c20,89. Most cytochrome c is localized to
cristae compartments20; OPA1 appears to regulate the
Rescued diameter of cristae junctions and therefore regulates
mitochondrion cytochrome c release 64,90. Overexpression of OPA1
Figure 5 | Mitochondrial dynamics protects mitochondrial function. a | In wild-type blocks cytochrome c release following the induction
Nature Reviews | Molecular Cell Biology of apoptosis by maintaining narrow cristae junctions64.
cells, the vast majority of mitochondria are functional (shown in green). In this simplified
diagram, one mitochondrion is depicted as non-functional (shown in orange). One of DRP1 has also been proposed to play a part in cristae
several possible reasons for dysfunction is a lack of mitochondrial DNA (mtDNA) remodelling during apoptosis91.
nucleoids (shown as black circles). The dysfunctional mitochondrion can regain its
function and mtDNA by fusing with a neighbouring mitochondrion. The fused Role in human disease
mitochondrion then undergoes fission, with both daughter mitochondria receiving Several human diseases are caused by mutations in genes
mtDNA nucleoids. It should be noted that the identities of the daughter mitochondria that are essential for mitochondrial dynamics (TABLE 1).
are distinct from the parental mitochondria, owing to content exchange and the fact
Each of these diseases causes degeneration of specific
that the fission point is typically distinct from the fusion point. b | In fusion-deficient
cells, mitochondria are fragmented due to ongoing fission in the absence of fusion.
nerves, reinforcing the notion that neurons are particularly
Mitochondria that lack mtDNA nucleoids accumulate because there is no pathway for prone to defects in mitochondrial dynamics.
defective mitochondria to regain mtDNA. Fusion-deficient cells can maintain mtDNA
nucleoids, but such nucleoids serve a much smaller mitochondrial mass. OPA1 and autosomal dominant optic atrophy.
Heterozygous mutations in OPA1 cause autosomal
dominant optic atrophy (ADOA), the most common
same time, mitochondrial outer membrane permeabilization heritable form of optic neuropathy92,93. This disease is
(MOMP) causes the release of contents of the inter- characterized by the degeneration of retinal ganglion
membrane space, such as cytochrome c and second cells, the axons of which form the optic nerve. More than
mitochondria-derived activator of caspase (SMAC)/ 100 pathogenic OPA1 mutations have been reported,
Diablo, into the cytoplasm. Because cytochrome c is with most occurring in the GTPase domain94. Half of the
preferentially sequestered in cristae compartments, mutants encode a truncated protein owing to a nonsense
it is thought that the opening of cristae junctions is mutation. A few nonsense mutations abolish nearly the
a vital step in facilitating its efficient release. Once in entire coding sequence, suggesting that haploinsufficiency
the cytosol, cytochrome c activates a cascade of caspases of OPA1 can cause ADOA. It remains possible that other,
that propagate and execute the apoptotic programme. less severe, truncations might have dominant-negative
These three structural changes — fragmentation, activity.
MOMP and cristae remodelling — occur at similar How these OPA1 mutations cause the clinical symp-
times, but their temporal sequence and causative links toms of ADOA remains to be clarified. Non-neuronal
Mitochondrial outer
membrane permeabilization
are still controversial80,81. cells from patients with ADOA can have aggregated, frag-
(MOMP). The opening of pores Mitochondrial fragmentation during apoptosis is mented or normal mitochondria93,95; however, because
in the mitochondrial outer associated with dynamic changes in the mitochondrial data from only a few patients have been reported, it is not
membrane — an early event localization of several proteins, including BAX, BAK, clear whether these findings are the norm. In addition,
during apoptosis that releases
MFN2, endophilin and DRP1 (Ref. 81). Inhibition of OPA1 mutations have been associated with reduced ATP
apoptotic factors from the
mitochondrial intermembrane fission activity blocks mitochondrial fragmentation, production and reduced mtDNA content96,97. The defects
space. reduces cytochrome c release and can reduce or delay that have been documented in human ADOA diseased
cell death depending on the experimental system46,82,83. tissue are not as severe as those observed in experimental
Haploinsufficiency In Caenorhabditis elegans and D. melanogaster, disrup- cells in which OPA1 is depleted. Fibroblasts that are defi-
A genetic state in diploids in
which a single functional copy
tion of DRP1 reduces the number of cell deaths84–86. cient for OPA1 have fragmented mitochondria, defects
of a gene is insufficient to In multiple systems, it seems that fission is important in respiration, aberrant cristae structure and increased
maintain a normal phenotype. for rapid and efficient cell death, although apoptosis susceptibility to apoptosis28,31,62,98.
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FURTHER INFORMATION
66. Minauro-Sanmiguel, F., Wilkens, S. & Garcia, J. J. (2006).
David C. Chan’s homepage:
Structure of dimeric mitochondrial ATP synthase: 88. Brooks, C. et al. Bak regulates mitochondrial
http://www.its.caltech.edu/~chanlab
novel F0 bridging features and the structural basis of morphology and pathology during apoptosis by
mitochondrial cristae biogenesis. Proc. Natl Acad. Sci. interacting with mitofusins. Proc. Natl Acad. Sci. USA All links are active in the online pdf
USA 102, 12356–12358 (2005). 104, 11649–11654 (2007).