Mitoregulin Contributes to Creatine Shuttling and Cardiolipin Protection in Mice Muscle

Author:

Averina Olga A.12,Permyakov Oleg A.1,Emelianova Mariia A.3,Grigoryeva Olga O.1,Lovat Maxim L.24,Egorova Anna E.5ORCID,Grinchenko Andrei V.6ORCID,Kumeiko Vadim V.56,Marey Maria V.7,Manskikh Vasily N.24,Dontsova Olga A.2389,Vysokikh Mikhail Yu.27ORCID,Sergiev Petr V.1238ORCID

Affiliation:

1. Institute of Functional Genomics, Lomonosov Moscow State University, 119992 Moscow, Russia

2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

3. Center for Life Sciences, Skolkovo Institute of Science and Technology, 143025 Moscow, Russia

4. Institute of Mitoengineering MSU, 119992 Moscow, Russia

5. Institute of Life Sciences and Biomedicine, Far Eastern Federal University, 690922 Vladivostok, Russia

6. A.V. Zhirmunsky National Scientific Center of Marine Biology, 690041 Vladivostok, Russia

7. Research Center for Obstetrics, Gynecology and Perinatology, 117198 Moscow, Russia

8. Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia

9. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119992 Moscow, Russia

Abstract

Small peptides compose a large share of the mitochondrial proteome. Mitoregulin (Mtln) is a mitochondrial peptide known to contribute to the respiratory complex I functioning and other processes in mitochondria. In our previous studies, we demonstrated that Mtln knockout mice develop obesity and accumulate triglycerides and other oxidation substrates in serum, concomitant with an exhaustion of tricarboxylic acids cycle intermediates. Here we examined the functional role of Mtln in skeletal muscles, one of the major energy consuming tissues. We observed reduced muscle strength for Mtln knockout mice. Decrease of the mitochondrial cardiolipin and concomitant increase in monolysocardiolipin concentration upon Mtln inactivation is likely to be a consequence of imbalance between oxidative damage and remodeling of cardiolipin. It is accompanied by the mitochondrial creatine kinase octamer dissociation and suboptimal respiratory chain performance in Mtln knockout mice.

Funder

Russian Science Foundation

Russian Ministry of Science and Higher Education

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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