MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation

Cell Rep. 2018 Jun 26;23(13):3701-3709. doi: 10.1016/j.celrep.2018.05.058.


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.

Keywords: fatty acid oxidation; metabolism; micropeptide; mitochondria; noncoding RNA; trifunctional protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Humans
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mitochondria, Heart / metabolism
  • Mitochondria, Muscle / metabolism*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Oxidation-Reduction
  • Sequence Alignment


  • Fatty Acids
  • Laptm4a protein, mouse
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Mtln protein, mouse