Related Experiment Video

Updated: Oct 21, 2025

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

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The mitochondrial permeability transition pore activates the mitochondrial unfolded protein response and promotes

Suzanne Angeli1, Anna Foulger1, Manish Chamoli1

  • 1Buck Institute for Research on Aging, Novato, United States.

Elife
|September 1, 2021
PubMed

Insights

Loss of OSCP, a mitochondrial protein, triggers the mitochondrial permeability transition pore (mPTP) and accelerates aging in adult worms. Inhibiting the mPTP or the mitochondrial unfolded protein response (UPRmt) restores lifespan, suggesting the mPTP promotes aging.

Area of Science:

  • Mitochondrial biology
  • Aging research
  • Molecular mechanisms of disease

Background:

  • Mitochondrial activity influences aging and chronic disease onset.
  • The mitochondrial permeability transition pore (mPTP), potentially formed by F-ATP synthase, is implicated in pathology.
  • OSCP, an F-ATP synthase subunit, normally prevents mPTP formation, but its role in aging is unknown.

Purpose of the Study:

  • To investigate the role of OSCP destabilization in aging.
  • To determine the contribution of the mitochondrial permeability transition pore (mPTP) to aging.
  • To explore the link between OSCP, mPTP, and the mitochondrial unfolded protein response (UPRmt) in aging.

Main Methods:

  • Utilized the nematode *Caenorhabditis elegans* as a model organism.
  • Investigated the effects of OSCP loss on lifespan and mPTP formation.
  • Examined the role of the mitochondrial unfolded protein response (UPRmt) in OSCP-deficient worms.
  • Employed pharmacological and genetic inhibition strategies for mPTP and UPRmt.

Main Results:

  • Loss of OSCP in *C. elegans* induced mPTP formation and shortened adult lifespan.
  • OSCP loss initiated the UPRmt, contributing to lifespan reduction.
  • Inhibiting the mPTP or UPRmt pharmacologically or genetically restored normal lifespan.
  • Loss of a key F-ATP synthase component extended adult lifespan, indicating mPTP promotes aging.

Conclusions:

  • The destabilization of OSCP initiates the mPTP and UPRmt, contributing to aging.
  • The mPTP/UPRmt pathway is a key nexus in aging and age-related diseases.
  • Inhibition of the UPRmt can be a protective strategy against aging under specific conditions.
Keywords:
C. elegansF-ATP synthaseagingc-subunitcell biologymitochondrial permeability transition poremitochondrial unfolded protein responseoscp/atp-3

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