The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.

Autor:	Vue Z; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Prasad P; Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801., Le H; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Neikirk K; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Harris C; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Garza-Lopez E; Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA., Wang E; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA., Murphy A; Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801., Jenkins B; Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801., Vang L; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Scudese E; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Shao B; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Kadam A; Department of Internal Medicine, Section of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA., Shao J; Central Microscopy Research Facility, University of Iowa, Iowa City, IA, 52242, USA., Marshall AG; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Crabtree A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Kirk B; Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA., Koh A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Wilson G; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Oliver A; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Rodman T; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Kabugi K; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Koh HJ; Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA., Smith Q; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, 92697, USA., Zaganjor E; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA., Wanjalla CN; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232., Dash C; Department of Biochemistry, Cancer Biology, Pharmacology and Neuroscience, Meharry Medical College, Nashville, TN, United States., Evans C; Department of Cell Biology, Duke University School of Medicine, Durham, NC, 27708, USA., Phillips MA; Department of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA., Hubert D; Department of Integrative Biology, Oregon State University, Corvallis, OR, 97331, USA., Ajijola O; UCLA Cardiac Arrhythmia Center, University of California, Los Angeles, CA, USA., Whiteside A; Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435 USA., Do Koo Y; Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.; Fraternal Order of Eagles Diabetes Research Center, Iowa City, Iowa, USA., Kinder A; Artur Sá Earp Neto University Center - UNIFASE-FMP, Petrópolis Medical School, Brazil., Demirci M; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232., Albritton CF; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.; Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208-3501, USA., Wandira N; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232., Jamison S; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232., Ahmed T; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232., Saleem M; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232., Tomar D; Department of Internal Medicine, Section of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA., Williams CR; Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH 45435 USA., Sweetwyne MT; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA., Murray SA; Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA., Cooper A; Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA., Kirabo A; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.; Vanderbilt Center for Immunobiology, Vanderbilt University, Nashville, TN, 37232, USA.; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University, Nashville, TN, 37232, USA.; Vanderbilt Institute for Global Health, Vanderbilt University, Nashville, TN, 37232, USA., Jadiya P; Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, NC., Quintana A; Department of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, Texas, USA., Katti P; National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.; Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, AP, 517619, India., Fu Dai D; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., McReynolds MR; Department of Biochemistry and Molecular Biology, The Huck Institute of the Life Sciences, Pennsylvania State University, State College, PA 16801., Hinton A Jr; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 12. Date of Electronic Publication: 2024 Jun 12.
DOI:	10.1101/2024.06.09.598108
Abstrakt:	The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health. Competing Interests: All authors have no competing interests. CONFLICT OF INTEREST The authors declare that they have no conflict of interest.
Databáze:	MEDLINE
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