Mitochondrial fission fueled by fasting

Wei Wong1

  • 1Science Signaling, AAAS, Washington, DC 20005, USA.

Science Signaling
|August 8, 2023
PubMed

Insights

Fasting activates the mTORC2 pathway, promoting mitochondrial fission and enhancing cellular respiration. This process supports overall mitochondrial function during periods of nutrient deprivation.

Area of Science:

  • Cellular Biology
  • Metabolism
  • Mitochondrial Dynamics

Background:

  • Mitochondrial dynamics, including fission and fusion, are crucial for cellular health.
  • The mechanistic target of rapamycin (mTOR) pathway plays a key role in regulating cellular metabolism and growth.
  • The specific role of mTOR complex 2 (mTORC2) in regulating mitochondrial dynamics during fasting remains incompletely understood.

Purpose of the Study:

  • To investigate the role of mTORC2 in regulating mitochondrial fission during fasting.
  • To determine how mTORC2 activation by fasting impacts mitochondrial respiration.

Main Methods:

  • Utilized cell culture models and animal models of fasting.
  • Employed biochemical assays to measure mTORC2 activity.
  • Assessed mitochondrial morphology using microscopy.
  • Quantified mitochondrial respiration through oxygen consumption rate measurements.

Main Results:

  • Fasting significantly activated mTORC2 signaling.
  • Activated mTORC2 promoted mitochondrial fission.
  • Increased mitochondrial fission correlated with enhanced mitochondrial respiration.
  • Inhibition of mTORC2 impaired fasting-induced mitochondrial fission and respiration.

Conclusions:

  • Fasting-induced mTORC2 activation is a key regulator of mitochondrial fission.
  • mTORC2-mediated mitochondrial fission supports enhanced mitochondrial respiration during fasting.
  • These findings highlight a novel mechanism by which cells adapt metabolically to nutrient deprivation.

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