Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes.

Autor: Shao B; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Killion M; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Oliver A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Vang C; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Zeleke F; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Neikirk K; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Vue Z; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Garza-Lopez E; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA., Shao JQ; Central Microscopy Research Facility, University of Iowa, Iowa City, Iowa, USA., Mungai M; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA., Lam J; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA., Williams Q; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Altamura CT; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Whiteside A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.; Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, Ohio, USA., Kabugi K; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., McKenzie J; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Ezedimma M; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Le H; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Koh A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Scudese E; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Vang L; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Marshall AG; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Crabtree A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Tanghal JI; Morehouse School of Medicine, Atlanta, Georgia, USA., Stephens D; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Koh HJ; Department of Biological Sciences, Tennessee State University, Nashville, Tennessee, USA., Jenkins BC; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, USA.; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA., Murray SA; Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Cooper AT; Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Williams C; Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, Ohio, USA., Damo SM; Department of Life and Physical Sciences, Fisk University, Nashville, Tennessee, USA., McReynolds MR; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, USA.; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA., Gaddy JA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; US Department of Veterans Affairs, Tennessee Valley Healthcare Systems, Nashville, Tennessee, USA., Wanjalla CN; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Beasley HK; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA., Hinton A Jr; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2024 Aug; Vol. 239 (8), pp. e31293. Date of Electronic Publication: 2024 May 21.
DOI: 10.1002/jcp.31293
Abstrakt: The sorting and assembly machinery (SAM) Complex is responsible for assembling β-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block-face-scanning electron microscopy and computer-assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50-deficient myotubes from mice and humans with wild-type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography-Mass Spectrometry-based metabolomics to explore differential changes in WT and Sam50-deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50-deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß-Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50-deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50-deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.
(© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: