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.
Which of the following can likely decrease muscle contraction?
A) The sarcoplasmic reticulum remains closed
B) Low concentration of calcium in the muscle fiber
C) Nonsense mutation in the gene that codes for troponin
D) All of the above
Correct answer: D. The question stem asks what can potentially
cause decreased muscle contraction, which means that every step from the
neuron-motor junction to the myosin-actin cross bridge, any malfunctions along
the way can cause this decreased muscle contraction. Investigating answer choice
A, if the sarcoplasmic reticulum remains closed, then the calcium will not be allowed
to escape it. Thus, the calcium will not be able to attach to the troponin, cause a
shift in tropomyosin, and allow actin to bind to myosin, creating the actin-myosin
cross bridge. Therefore, if the sarcoplasmic reticulum decides to remain closed,
then there would be no cross bridge forming, decreasing muscle contraction. There,
option choice A is correct.
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