Day 97 MCAT Practice Question

Passage 9: Mitochondria

Mitochondria are the primary source of energy production and are implicated in a

wide range of biological processes in most eukaryotic cells. Skeletal muscle heavily

relies on mitochondria for energy supplements. In addition to being a powerhouse,

mitochondria evoke many functions in skeletal muscle, including regulating

calcium and reactive oxygen species levels. A healthy mitochondria population is

necessary for the preservation of skeletal muscle homeostasis, while mitochondrial

dysregulation is linked to numerous myopathies.



Mitochondria generates energy in the form of adenosine triphosphate (ATP) from

energy-enriched molecules such as pyruvate, fatty acids, and amino acids via

oxidative phosphorylation. Electrons generated from oxidations of energy-enriched

molecules are transferred via nicotinamide adenine dinucleotide hydrogen (NADH)

to complex I (NADH ubiquinone oxidoreductase) or flavin adenine dinucleotide

(FADH2) to complex II (succinate dehydrogenase), then transported to coenzyme

Q. Coenzyme Q then delivers electrons generated from complex I or II via complex

III (cytochrome bc1 complex) to cytochrome c and then to complex IV (cytochrome

c oxidase), where oxygen is reduced to water. Finally, coupling with electron

generation, the protons (H+) are pumped to the intermembrane space from

complex I, III, and IV for ATP production in complex V (ATP synthase).



In addition to ATP generation, mitochondria have other functions, including

the production of reactive oxygen species (ROS) and the regulation of cellular

calcium homeostasis. Mitochondrial ROS is the side product of the incomplete

mitochondrial oxidative phosphorylation process from the electron leakage

predominately in complexes I and III. Excess ROS damages cells by oxidation of

nucleic acids, proteins, and lipids. Yet, the growing evidence reveals that ROS acts

as a secondary messenger that participates in a wide range of cell signaling to

stimulate cell proliferation, differentiation, death, etc.



Mitochondria in skeletal muscle form a dynamic network, named mitochondrial

reticulum, to minimize metabolite distribution and maximize energy utilization

efficiency. The mitochondrial reticulum is constantly reshaped by fusion and fission

events, allowing mitochondria to exchange their content, including mitochondrial

DNA (mtDNA). This is shown in Figure 1.



The control of skeletal muscle is voluntary by motor neurons to generate force

and locomotion. The coordination of differences in nerve impulse transmission,

membrane excitability, excitation–contraction coupling calcium flux between

sarcoplasmic reticulum and cytosol, and ATP hydrolysis rate of myosin ATPase

generates a variety of movements in our daily life. Most, if not all, of the cellular

actions controlling movement are highly dependent on mitochondrial activities. It

was not surprising that the common feature of mitochondrial diseases is muscle

dysfunction.

If a researcher performs an experiment and finds that there is a significantly

large amount of mitochondrial ROS and finds that two of the complexes in the

ETC are only half functional, which of the following might be a direct side effect?

A) Increased ATP production

B) Decreased ADP in the mitochondrial matrix

C) Decrease production of Fumarate

D) Decreased production of Succinyl-CoA