MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation
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 cr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718308222 |
| _version_ | 1831727901413736448 |
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| author | Catherine A. Makarewich Kedryn K. Baskin Amir Z. Munir Svetlana Bezprozvannaya Gaurav Sharma Chalermchai Khemtong Akansha M. Shah John R. McAnally Craig R. Malloy Luke I. Szweda Rhonda Bassel-Duby Eric N. Olson |
| author_facet | Catherine A. Makarewich Kedryn K. Baskin Amir Z. Munir Svetlana Bezprozvannaya Gaurav Sharma Chalermchai Khemtong Akansha M. Shah John R. McAnally Craig R. Malloy Luke I. Szweda Rhonda Bassel-Duby Eric N. Olson |
| author_sort | Catherine A. Makarewich |
| collection | DOAJ |
| description | 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. : Micropeptide regulator of β-oxidation (MOXI) is encoded by a muscle-enriched RNA transcript misannotated as non-coding. MOXI localizes to the inner mitochondrial membrane where it interacts with the trifunctional protein to modulate fatty acid β-oxidation and exercise capacity. Keywords: micropeptide, fatty acid oxidation, metabolism, mitochondria, trifunctional protein, noncoding RNA |
| first_indexed | 2024-12-21T06:39:23Z |
| format | Article |
| id | doaj.art-7104ce443c914948b23d40e5e3e40066 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T06:39:23Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7104ce443c914948b23d40e5e3e400662022-12-21T19:12:46ZengElsevierCell Reports2211-12472018-06-01231337013709MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-OxidationCatherine A. Makarewich0Kedryn K. Baskin1Amir Z. Munir2Svetlana Bezprozvannaya3Gaurav Sharma4Chalermchai Khemtong5Akansha M. Shah6John R. McAnally7Craig R. Malloy8Luke I. Szweda9Rhonda Bassel-Duby10Eric N. Olson11Department of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding authorSummary: 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. : Micropeptide regulator of β-oxidation (MOXI) is encoded by a muscle-enriched RNA transcript misannotated as non-coding. MOXI localizes to the inner mitochondrial membrane where it interacts with the trifunctional protein to modulate fatty acid β-oxidation and exercise capacity. Keywords: micropeptide, fatty acid oxidation, metabolism, mitochondria, trifunctional protein, noncoding RNAhttp://www.sciencedirect.com/science/article/pii/S2211124718308222 |
| spellingShingle | Catherine A. Makarewich Kedryn K. Baskin Amir Z. Munir Svetlana Bezprozvannaya Gaurav Sharma Chalermchai Khemtong Akansha M. Shah John R. McAnally Craig R. Malloy Luke I. Szweda Rhonda Bassel-Duby Eric N. Olson MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation Cell Reports |
| title | MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation |
| title_full | MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation |
| title_fullStr | MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation |
| title_full_unstemmed | MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation |
| title_short | MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation |
| title_sort | moxi is a mitochondrial micropeptide that enhances fatty acid β oxidation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718308222 |
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