Meeting Abstract

27.3  Wednesday, Jan. 4  Can spatial variation in mitochondrial degradation predict mitochondrial distribution in skeletal muscle? PATHI, B.; KINSEY, S.T.*; HOWDESHELL, M.E.; PRIESTER, C.; MCNEILL, R.S.; LOCKE, B.R. ; Florida State Univ.; UNC Wilmington; UNC Wilmington; UNC Wilmington; UNC Wilmington; Florida State Univ. kinseys@uncw.edu

Mitochondrial density is governed by the balance between biogenesis and degradation in skeletal muscle. However, there is no paradigm to explain the heterogeneous distribution of mitochondria, which presumably arises from spatial variation in signals that govern biogenesis and degradation. However, mitochondrial biogenesis relies on gene expression in both mitochondria and nuclei, so spatial variation in biogenesis signals is lost as the signal is propagated through the nucleus. In contrast, growing evidence suggests that mitochondria are selectively degraded via targeted mitophagy, which can be induced by low oxygen. We tested the hypotheses that (1) mitochondrial distribution in skeletal muscle is governed by biogenesis that is homogeneous across the fiber and degradation that is spatially variable and dependent on oxygen concentration, and (2) that the heterogeneous distribution of mitochondria yields a higher energetic state and greater aerobic capacity than a uniform distribution. We measured fiber size, capillarity and mitochondrial distribution in red and white fibers of dolphinfish, in white fibers that undergo a large increase in size during hypertrophic growth in black sea bass, and in 4 skeletal muscle fiber types in mouse. We compared these distributions to those predicted by a coupled mathematical model of skeletal muscle that included a reaction-diffusion model of aerobic metabolism and a cellular automata model of mitochondrial biogenesis and degradation. The model effectively predicted the observed distributions, and showed that the heterogeneous distribution of mitochondria led to a higher cellular energy state and greater aerobic capacity.