Stein 2018 Cell Rep

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Publications in the MiPMap
Stein CS, Jadiya P, Zhang X, McLendon JM, Abouassaly GM, Witmer NH, Anderson EJ, Elrod JW, Boudreau RL (2018) Mitoregulin: A lncRNA-encoded microprotein that supports mitochondrial supercomplexes and respiratory efficiency. Cell Rep 23:3710-20.

Β» PMID: 29949756 Open Access

Stein CS, Jadiya P, Zhang X*, McLendon JM, Abouassaly GM, Witmer NH, Anderson EJ, Elrod JW, Boudreau RL (2018) Cell Rep

Abstract: Mitochondria are composed of many small proteins that control protein synthesis, complex assembly, metabolism, and ion and reactive oxygen species (ROS) handling. We show that a skeletal muscle- and heart-enriched long non-coding RNA, LINC00116, encodes a highly conserved 56-amino-acid microprotein that we named mitoregulin (Mtln). Mtln localizes to the inner mitochondrial membrane, where it binds cardiolipin and influences protein complex assembly. In cultured cells, Mtln overexpression increases mitochondrial membrane potential, respiration rates, and Ca2+ retention capacity while decreasing mitochondrial ROS and matrix-free Ca2+. Mtln-knockout mice display perturbations in mitochondrial respiratory (super)complex formation and activity, fatty acid oxidation, tricarboxylic acid (TCA) cycle enzymes, and Ca2+ retention capacity. Blue-native gel electrophoresis revealed that Mtln co-migrates alongside several complexes, including the complex I assembly module, complex V, and supercomplexes. Under denaturing conditions, Mtln remains in high-molecular-weight complexes, supporting its role as a sticky molecular tether that enhances respiratory efficiency by bolstering protein complex assembly and/or stability.

β€’ Bioblast editor: Plangger M, Kandolf G β€’ O2k-Network Lab: US NC Greenville Anderson EJ

Labels: MiParea: Respiration, mt-Membrane, nDNA;cell genetics, Genetic knockout;overexpression 

Organism: Human  Tissue;cell: Heart, Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Supercomplex 

Coupling state: LEAK, OXPHOS  Pathway: F, N  HRR: Oxygraph-2k 

Labels, 2018-08 

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