Full Citation

Berezhnov, A. V.; Soutar, M. P. M.; Fedotova, E. I.; Frolova, M. S.; Plun-Favreau, H.;
Zinchenko, V. P.; Abramov, A. Y. Intracellular PH Modulates Autophagy and Mitophagy. Journal
of Biological Chemistry. 2016, 291, 87018708.
Section Headings
Abstract
Experimental Procedures
Results
Discussion
Definitions of Keywords
Uncoupler (specifically FCCP): collapses the proton gradient by transporting hydrogen ions
through the membrane before they are used for ATP synthesis.
Neurodegenerative disease: incurable diseases that cause loss of function of neurons; we talked
about these with ROS.
Ubiquitination: the covalent attachment of ubiquitin to degrading proteins.
Autophagy (mitophagy): cellular degradation pathway in which damaged organelles are broken
down.
Lysosomes: an organelle that uses certain enzymes to degrade damaged cell components.

This articles main objective was to better understand the physiological and pathological
triggers of mitophagy (autophagy of the mitochondria). One of the motivations for this research
was that mitophagy is thought to contribute to some neurodegenerative diseases such as
Parkinsons. Specifically, this research looks into FCCP and nigericin causing mitophagy and
reducing their effects by manipulating intracellular pH by monensin. It is concluded that an
increase of intracellular pH is effective in slowing the process of mitochondrial degradation.
It makes sense that mitochondrial degradation would be very damaging to the cell
system, as the mitochondria are responsible for much of the ATP production of a cell. This
articles mentions that defective mitophagy can lead to cell death pathways. I dont completely
understand all of the chemistry behind it, but I believe that some component, Parkin, present in
people with Parkinsons, causes abnormal mitophagy, which in turn results in cell death
pathways. It was found that low concentrations of FCCP result in a complete loss of
mitochondrial membrane potential, which doesnt allow mitophagy, while a high concentration
of FCCP acidifies intracellular pH, leading to mitophagy. Other physiological processes such as
starvation also lead to acidification of the cell, resulting in mitophagy.
Unfortunately, I was not able to make sense of much of the experimental procedures of
this article because there were many unspecified abbreviations and methods I am unfamiliar
with. However, I definitely think I understand the overall conclusions, motivations, and process
of the research. One important concept I was able to take away from this article is that FCCP, an
uncoupler, effects intracellular pH because it results in the transportation of hydrogen ions across
the cellular membrane, causing a pH alteration. It was interesting to see the research process and
uncertain conclusions that can be gleaned from this research because while this group was able
to prove that manipulation of pH by monensin dissipates the effects of FCCP and nigericin on
mitophagy, they were unable to directly link this to any breakthrough treatment of Parkinsons
disease. While this was unsurprising to me because I have heard many times that research is very
much a slowly working process of adding to findings with every proceeding project, it was
interesting to read a specific example of a successful hypothesis with, for now, seemingly
insignificant results that may in the future prompt another experimentation that leads to
successful treatment of fatal diseases. There is still clearly much to be known on this subject and
many other manipulations and variables to consider.
When I began looking for articles, I was at first very overwhelmed with all of the
terminology I was unfamiliar with, and I doubted I would be able to make sense of much of the
content. However, after reading a few abstracts when I was choosing which to stick with, I was
surprised at how much I was taking away from each, despite my lack of background knowledge.
Another thing I struggled with in this assignment was actually using the research databases and
finding how to manipulate my searches to find a relevant article. This is something I have not yet
had to do for other classes, and I think it is an important skill. I have recently begun doing
undergraduate research in a lab and will be doing my own research project next year on powderliquid contact angle determination, so finding applicable current research on my topic next year
will be very helpful in crafting my own methods and specifics of the project. I found that many
current articles are on cancer research, and it was interesting to me how much I was able to
understand when browsing over the abstracts of cancer research articles.