학술논문
CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.
Document Type
Academic Journal
Author
Nechushtai R; Plant & Environmental Sciences, The Alexander Silberman Institute of Life Science and The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Edmond J. Safra Campus at Givat Ram, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.; Rowland L; Department of Surgery, University of Missouri School of Medicine, Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65201.; Karmi O; Plant & Environmental Sciences, The Alexander Silberman Institute of Life Science and The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Edmond J. Safra Campus at Givat Ram, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.; Marjault HB; Department of Surgery, University of Missouri School of Medicine, Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65201.; Nguyen TT; Gehrke Proteomics Center, Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211.; Mittal S; Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080.; Ahmed RS; Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080.; Grant D; Electron Microscopy Core Facility, University of Missouri, NextGen Precision Health Institute, Columbia, MO 65211.; Manrique-Acevedo C; Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO 65201.; NextGen Precision Health, University of Missouri, Columbia, MO 65201.; Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201.; Morcos F; Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080.; Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080.; Department of Physics, University of Texas at Dallas, Richardson, TX 75080.; Center for Systems Biology, University of Texas at Dallas, Richardson, TX 75080.; Onuchic JN; Center for Theoretical Biological Physics, Rice University, Houston, TX 77005.; Department of Physics and Astronomy, Rice University, Houston, TX 77005.; Department of Chemistry, Rice University, Houston, TX 77005.; Department of Biosciences, Rice University, Houston, TX 77005.; Mittler R; Department of Surgery, University of Missouri School of Medicine, Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65201.
Source
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Subject
Language
English
Abstract
Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration. Although the function of the outer mitochondrial CISD/NEET proteins, CISD1/mitoNEET and CISD2/NAF-1, has been defined in skeletal muscle cells, the role of the inner mitochondrial CISD protein, CISD3/MiNT, is currently unknown. Here, we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne muscular dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscles, as well as their mitochondria, and that CISD3 interacts with, and donates its [2Fe-2S] clusters to, complex I respiratory chain subunit NADH Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2). Using coevolutionary and structural computational tools, we model a CISD3-NDUFV2 complex with proximal coevolving residue interactions conducive of [2Fe-2S] cluster transfer reactions, placing the clusters of the two proteins 10 to 16 Å apart. Taken together, our findings reveal that CISD3/MiNT is important for supporting the biogenesis and function of complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact different muscle degeneration syndromes, aging, and related conditions.
Competing Interests: Competing interests statement:The authors declare no competing interest.
Competing Interests: Competing interests statement:The authors declare no competing interest.