Effects of MOTS-c on the mitochondrial function of cells harboring 3243 A to G mutant mitochondrial DNA

Chang Ho Ahn1,2, Eun Hye Choi1,2, Byung Soo Kong1,2

  • 1Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Insights

Mitochondrial derived peptides (MDPs) like MOTS-c do not improve mitochondrial dysfunction in cells with mutant mitochondrial DNA. This suggests that different MDPs have varied effects on cellular health.

Area of Science:

  • Mitochondrial biology
  • Molecular genetics
  • Cellular metabolism

Background:

  • Mitochondrial derived peptides (MDPs) are encoded by mitochondrial DNA and play roles in cellular processes.
  • MOTS-c and Humanin are examples of MDPs with known functions in metabolism and cytoprotection.
  • The effect of MOTS-c on mitochondrial function, particularly in the context of mitochondrial dysfunction, remains largely unexplored.

Purpose of the Study:

  • To investigate the impact of both exogenous and endogenous MOTS-c on mitochondrial function.
  • To assess MOTS-c's effects in a cybrid cell model harboring the 3243 A to G mutant mitochondrial DNA, a known cause of mitochondrial dysfunction.
  • To compare MOTS-c's efficacy with other MDPs in improving mitochondrial health.

Main Methods:

  • Utilized a cybrid cell model with 3243 A to G mutant mitochondrial DNA.
  • Administered exogenous synthetic MOTS-c to the mutant cybrid cells.
  • Transfected mutant cybrid cells with a MOTS-c EGFP expression vector to study endogenous MOTS-c effects.
  • Assessed ATP content, mitochondrial complex mRNA and protein levels, and mitochondrial respiration (basal and stimulated).

Main Results:

  • Exogenous MOTS-c did not significantly alter ATP levels, mitochondrial complex expression, or mitochondrial respiration in mutant cybrid cells.
  • Stable expression of endogenous MOTS-c via transfection also failed to improve ATP production or mitochondrial complex function.
  • MOTS-c did not ameliorate the mitochondrial dysfunction observed in the cybrid cells with mutant mitochondrial DNA.

Conclusions:

  • MOTS-c does not appear to improve mitochondrial dysfunction in cells with the 3243 A to G mutant mitochondrial DNA.
  • Unlike other known MDPs, MOTS-c does not exhibit a beneficial effect on mitochondrial function in this specific cellular model.
  • These findings highlight the heterogeneous functional properties among different mitochondrial derived peptides.

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