ASSESSMENT OF MITOCHONDRIAL ENERGETICS IN A SKELETAL MUSCLE RESISTANT TO HYPOXIA.

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Serena Mooney (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Skeletal muscle is dependent upon oxygen (O2) to maintain normal physiological function by acting as the final electron acceptor in the mitochondria during ATP production. Loss of O2 tension (i.e. hypoxia) leads to the collapse of the mitochondria resulting in myopathy development that is seen in various health conditions including peripheral arterial disease and dystrophy. Hypoxia induces a severe muscle pathology that can lead to complete loss of function ultimately contributing to increased mortality. We recently identified a mammalian muscle, the flexor digitorum brevis (FDB), that functions without O2. No other muscle has the unique ability of the FDB, and it suggests that the FDB is not dependent upon mitochondria to function. To test this possibility, we compared mitochondrial bioenergetic function of two different mouse peripheral skeletal muscles, the extensor digitorum longus (EDL) and flexor digitorum brevis (FDB). Initially, we assessed mitochondrial energetics using permeabilized muscle fiber bundles (PMFB) from adult mice which allows us to measure mitochondrial function without disruption of the reticular organelle structure. We found that PMFBs from the FDB exhibit significantly lower mitochondrial O2 respiration compared to the PMFBs EDL muscle. To confirm this finding, we sought to make these measures in isolated mitochondria. Due to the small size of the muscles, we developed a new approach for isolating mitochondria. EDL and FDB muscles were removed from adult mice and mitochondria were isolated from each muscle. Mitochondrial O2 respiration and membrane potential were measured using an approach that mimics energetic conditions in a physiological manner. The data confirmed a lower mitochondrial respiratory capacity in the FDB compared to EDL even under normalized conditions. Further, when compared to the EDL muscle the data suggest that mitochondria within the FDB are poorly developed and are unlikely capable of preventing a significant energetic stress. These data appear to confirm that unlike any other mammalian skeletal muscle, the FDB has evolved to operate without oxygen or mitochondria and is reliant on alternative metabolic pathways to provide ATP for the muscle. Future studies will seek to determine the metabolic pathways the FDB utilizes to provide energy for physiological function.

Additional Information

Publication

Thesis

Language: English

Date: 2023

Subjects

skeletal muscle;physiology;hypoxia resistant tissue

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