期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 600, 期 3, 页码 547-567出版社
WILEY
DOI: 10.1113/JP282153
关键词
allometry; inter-organelle interactions; metabolism; mitochondria; reticulum
资金
- National Institutes of Health NHLBI intramural funds (RSB) National Institutes of Health NCI [CA207287]
Mitochondrial adaptations are essential for cell function and energy balance in mammals, but the mechanisms behind these adaptations are still poorly understood. In this study, we used a model of extreme mammalian metabolism, the least shrew, to investigate mitochondrial morphology and protein composition in different organs. We found that organs with similar metabolic demand have distinct mitochondrial adaptations, suggesting that the topology of energy utilization plays a role in these adaptations.
Mitochondrial adaptations are fundamental to differentiated function and energetic homeostasis in mammalian cells. But the mechanisms that underlie these relationships remain poorly understood. Here, we investigated organ-specific mitochondrial morphology, connectivity and protein composition in a model of extreme mammalian metabolism, the least shrew (Cryptotis parva). This was achieved through a combination of high-resolution 3D focused ion beam electron microscopy imaging and tandem mass tag mass spectrometry proteomics. We demonstrate that liver and kidney mitochondrial content are equivalent to the heart, permitting assessment of mitochondrial adaptations in different organs with similar metabolic demand. Muscle mitochondrial networks (cardiac and skeletal) are extensive, with a high incidence of nanotunnels - which collectively support the metabolism of large muscle cells. Mitochondrial networks were not detected in the liver and kidney as individual mitochondria are localized with sites of ATP consumption. This configuration is not observed in striated muscle, likely due to a homogeneous ATPase distribution and the structural requirements of contraction. These results demonstrate distinct, fundamental mitochondrial structural adaptations for similar metabolic demand that are dependent on the topology of energy utilization process in a mammalian model of extreme metabolism.
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