[Catalyst 2019]

The Mitochondria
More Than Just the Powerhouse of the Cell
By Tasneem Mustafa
No matter how much or how little
experience you have with biology,
most of us know one thing:
mitochondria are the powerhouses
of the cell. While this has become a fun
catchphrase to help us remember the
components of a cell, the statement runs
true for a reason: mitochondria are crucial
for the production of adenosine triphosphate
(ATP) – the “energy currency of life” – by
processing sugar from the food that we
consume. However, “powerhouse” is a gross
simplification of the capabilities of this small
organelle, as mitochondria are central to
countless processes such as calcium signaling,
growth signaling, metabolic production, and
activation of multiple cell death pathways.
Here at Rice, mitochondria play a central
role in the research of Dr. Natasha Kirienko,
a professor of Biosciences, as she is
investigating mitochondria’s role in signaling
pathways, which could lead to larger, possibly
life-saving, implications.
Here on campus, Dr. Kirienko runs what
she affectionately refers to as the “worm
lab” as so much of her research has
revolved around the model organism C.
elegans. In fact, C. elegans is a species of
roundworm that is extremely useful in a
laboratory setting, which, according to the
University of Minnesota, “shares many of
the essential biological characteristics that
are central problems of human biology.”
In C. elegans, it is easier to track different
processes such as the mitochondrial damage
pathway illustrated in Figure 1. Healthy
mitochondria are essential to a healthy cell,
as the energy produced through oxidative
phosphorylation of ATP in the mitochondria
fuels the rest of the cell. However, if the
mitochondria are afflicted, the mitochondrial
surveillance pathways will be activated
to attempt salvaging the cell. However,
sometimes the deterioration of mitochondria
continues, preventing the cell from achieving
homeostasis as more functions fail. At this
point, the deteriorated cells will experience
a mitochondrial membrane potential drop
that signifies cell death and makes it a
target for recycling via mitophagy. Recycling
mitochondria may seem like an effective
mechanism to conserve resources, but a
different set of problems can arise. Proteins
can escape from the mitochondria and
end up in the cytosol, which could trigger
apoptosis or cell self-destruction. Dr. Kirienko
further details that the “overactivation of
autophagy will also trigger [a] whole cell
autophagy”, demonstrating how big of an
effect mitochondria can have. Because
of these effects and more, mitochondrial
damage can have dangerous impacts as
this amplification can lead to extensive, and
oftentimes irreversible, cellular level damage
The study of mitochondrial pathways piqued
Dr. Kiriendo’s interest long before she started
her research at Rice. As a graduate student,
she studies mitochondrial mutations in
C. elegans and found a mutant “that was
sensitive to all kinds of stresses...because it
cannot activate [its] ESRE genes”. The Ethanol
and Stress Response Element, or ESRE, that as
Dr. Kirienko explained, can“mitigate damage
from a variety of abiotic stresses”, and though
commonly triggered by ethanol, can also be
triggered by other stressors. So, the mutant
that Dr. Kirienko had found gave the first
hint that there was a connection between
ESRE and mitochondrial mutations. Through
further research, Dr. Kirienko realized that the
ESRE genes can be triggered by mitochondrial
damage due to its connection with “ethanol,
hypoxia, oxidative stress, and pseudomonas,
a common bacteria behind infections, and
iron removal by pseudomonas”. However,
more research needs to be done to further
our understanding of the mechanisms,
especially of the transcription factors,
as they are heavily involved in the in the
signal transduction cascade that starts the
mitochondrial damage.
Interestingly, while Dr. Kirienko’s lab has
always been known as the “worm lab” at
Rice, she is currently shifting her focus from
C. elegans to mammalian cells, which could
be more beneficial for potential cancer
research because they have more similarities
with human cells than C. elegans cells. As
an aid to her future research goals, a fiveyear
grant for nearly $2 million dollars from
the National Institute of General Medical
Sciences to investigate the ESRE pathway and
its mitochondria-repairing mechanisms has
been awarded to Dr. Kirienko. Additionally,
Dr. Kirienko believes that the most effective
way to carry out her research is by continuing
her cross disciplinary research approach. By
integrating different areas of research with
a “biochemical and genetic approach”, Dr.
Kirienko can develop a more comprehensive
picture about mitochondrial repairing
mechanisms. By using bioinformatics, the
Kirienko lab mines large data specifically
available for cancer-related research to
generate a list of genetic mutations and
compare those results with their projects on
C. elegans and mammalian cells. By utilizing
different approaches, Dr. Kirienko’s team can
move forward in their research and into the
world of cancer research.
The mitochondrian plays a crucial role in the
overall health of a cell. We are on the cusp of
learning more about the ESRE pathway and
the role it plays in mitochondrial damage.
If we can find a way to stop or slow down
mitochondrial damage, it will greatly mitigate
the damage as the cell will be more likely to
recover. If we can gain the reins of control
for mitochondria, it might just be the key to
defeating cancer. No wonder mitochondria
are called the powerhouse of the cell.
Repair
Mitochondrial
Surveillance
+ chaperone expression
- translation
Remove
DESIGN BY Krithika Kumar
EDITED BY Yvonne Chien
Healthy
Mitochondria (MT)
Sick
Mitochondria
mitophagy
apoptosis
CATALYST | 19