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.
According to the passage, mitochondria dysregulation is linked to numerous
myopathies. If an individual has mitochondrial disease and their mitochondria
only function at half capacity, what will likely be one of the mentioned
myopathies?
A) The myosin-actin cross bridge will detach less strongly after the power stroke.
B) The myosin-actin cross bridge will detach less frequently after the power
stroke.
C) The power stroke of the myosin-actin cross-bridge will not be as strong
D) The power stroke of the myosin-actin cross-bridge will not be as frequent
Correct answer: B. According to the passage, mitochondrial diseases
have been associated with muscle dysfunction multiple times. One reason for this
is that mitochondria produce most of the ATP that we use for energy. In order for
the muscle to contract, it needs the necessary anatomical components, along with
calcium, ATP, and ADP. If there is a significant disruption in ATP production via the
mitochondrial disease, muscle contraction would be disrupted. More specifically,
when the mitochondria are defective, and there is less ATP present, this will affect
the actin-myosin cross-bridge cycle. The step that requires ADP and phosphate
is when the actin-myosin cross-bridge performs a power stroke. The step that
requires ATP is when the actin-myosin cross-bridge detaches from each other.
Therefore, if the mitochondria are defective, then this step of detachment will not
occur as frequently because there is less ATP available. Since detachment is an allor-nothing event, the notion of strong detachment versus light detachment should
be dismissed. Instead, if there is a low transient level of ATP available, then it will
detach as many cross bridges as it can, but since there is less ATP, the number of
cross-bridges broken will be a lower number. Therefore, B is the right answer.
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