MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid b-Oxidation
| Autor: | John R. McAnally, Luke I. Szweda, Amir Z. Munir, Craig R. Malloy, Kedryn K. Baskin, Rhonda Bassel-Duby, Eric N. Olson, Gaurav Sharma, Catherine A. Makarewich, Akansha M. Shah, Chalermchai Khemtong, Svetlana Bezprozvannaya |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Enzyme complex Physiology Transgene Mice Transgenic Mitochondrial trifunctional protein Mitochondrion General Biochemistry Genetics and Molecular Biology Article Mitochondria Heart 60104 Cell Metabolism Mitochondrial Proteins 03 medical and health sciences Mice Animals Humans Amino Acid Sequence Inner mitochondrial membrane Beta oxidation lcsh:QH301-705.5 chemistry.chemical_classification Mice Knockout biology Fatty Acids Fatty acid Membrane Transport Proteins 60802 Animal Cell and Molecular Biology Cell biology Mitochondria Muscle Mice Inbred C57BL 030104 developmental biology chemistry lcsh:Biology (General) FOS: Biological sciences Knockout mouse biology.protein 60603 Animal Physiology - Systems Oxidation-Reduction Sequence Alignment |
| Zdroj: | Cell reports Cell Reports, Vol 23, Iss 13, Pp 3701-3709 (2018) |
| DOI: | 10.25376/hra.7795601 |
| Popis: | SUMMARY Micropeptide regulator of β-oxidation (MOXI) is a conserved muscle-enriched protein encoded by an RNA transcript misannotated as non-coding. MOXI localizes to the inner mitochondrial membrane where it associates with the mitochondrial trifunctional protein, an enzyme complex that plays a critical role in fatty acid β-oxidation. Isolated heart and skeletal muscle mitochondria from MOXI knockout mice exhibit a diminished ability to metabolize fatty acids, while transgenic MOXI overexpression leads to enhanced β-oxidation. Additionally, hearts from MOXI knockout mice preferentially oxidize carbohydrates over fatty acids in an isolated perfused heart system compared to wild-type (WT) animals. MOXI knockout mice also exhibit a profound reduction in exercise capacity, highlighting the role of MOXI in metabolic control. The functional characterization of MOXI provides insight into the regulation of mitochondrial metabolism and energy homeostasis and underscores the regulatory potential of additional micropeptides that have yet to be identified. In Brief Micropeptide regulator of b-oxidation (MOXI) is encoded by a muscle-enriched RNA transcript misannotated as noncoding. MOXI localizes to the inner mitochondrial membrane where it interacts with the trifunctional protein to modulate fatty acid b-oxidation and exercise capacity. Graphical Abstract |
| Databáze: | OpenAIRE |
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