Metabolic design in a model of extreme mammalian metabolism, the North American least shrew (Cryptotis parva)

May 01, 2021

Dillon J. Chung (1), Grey P. Madison (1), Angel M. Aponte (1), Komudi Singh (1) , Yuesheng Li (1), Mehdi Pirooznia (1), Christopher K. E. Bleck (1), Nissar A. Darmani (2), Robert S. Balaban (1)
bioRxiv, May 2021. DOI: 10.1101/2021.05.28.446190


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 EM imaging and tandem-mass-tag MS 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 homogenous 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.

How Our Software Was Used

Dragonfly was used to segment organelles and cells.

Author Affiliation

(1) National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA 20892.
(2)Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA 91766.