MCJ/DnaJC15, an endogenous mitochondrial repressor of the respiratory chain that controls metabolic alterations

Mol Cell Biol. 2013 Jun;33(11):2302-14. doi: 10.1128/MCB.00189-13. Epub 2013 Mar 25.


Mitochondria are the main engine that generates ATP through oxidative phosphorylation within the respiratory chain. Mitochondrial respiration is regulated according to the metabolic needs of cells and can be modulated in response to metabolic changes. Little is known about the mechanisms that regulate this process. Here, we identify MCJ/DnaJC15 as a distinct cochaperone that localizes at the mitochondrial inner membrane, where it interacts preferentially with complex I of the electron transfer chain. We show that MCJ impairs the formation of supercomplexes and functions as a negative regulator of the respiratory chain. The loss of MCJ leads to increased complex I activity, mitochondrial membrane potential, and ATP production. Although MCJ is dispensable for mitochondrial function under normal physiological conditions, MCJ deficiency affects the pathophysiology resulting from metabolic alterations. Thus, enhanced mitochondrial respiration in the absence of MCJ prevents the pathological accumulation of lipids in the liver in response to both fasting and a high-cholesterol diet. Impaired expression or loss of MCJ expression may therefore result in a "rapid" metabolism that mitigates the consequences of metabolic disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Respiration / genetics
  • Cholesterol / adverse effects
  • Diet
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Fatty Liver / genetics
  • Female
  • Gene Expression Regulation
  • HSP40 Heat-Shock Proteins / genetics*
  • Humans
  • Intracellular Membranes / metabolism
  • Lipid Metabolism / genetics*
  • Male
  • Membrane Potential, Mitochondrial / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Rotenone / pharmacology


  • DNAJC15 protein, human
  • HSP40 Heat-Shock Proteins
  • Mcj protein, mouse
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Repressor Proteins
  • Rotenone
  • Adenosine Triphosphate
  • Cholesterol
  • Electron Transport Complex I