The mitochondrial permeability transition pore: an evolving concept critical for cell life and death

Biol Rev Camb Philos Soc. 2021 Dec;96(6):2489-2521. doi: 10.1111/brv.12764. Epub 2021 Jun 21.

Abstract

In this review, we summarize current knowledge of perhaps one of the most intriguing phenomena in cell biology: the mitochondrial permeability transition pore (mPTP). This phenomenon, which was initially observed as a sudden loss of inner mitochondrial membrane impermeability caused by excessive calcium, has been studied for almost 50 years, and still no definitive answer has been provided regarding its mechanisms. From its initial consideration as an in vitro artifact to the current notion that the mPTP is a phenomenon with physiological and pathological implications, a long road has been travelled. We here summarize the role of mitochondria in cytosolic calcium control and the evolving concepts regarding the mitochondrial permeability transition (mPT) and the mPTP. We show how the evolving mPTP models and mechanisms, which involve many proposed mitochondrial protein components, have arisen from methodological advances and more complex biological models. We describe how scientific progress and methodological advances have allowed milestone discoveries on mPTP regulation and composition and its recognition as a valid target for drug development and a critical component of mitochondrial biology.

Keywords: calcium; cell death; mitochondria; mitochondrial permeability transition pore.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins* / metabolism
  • Mitochondrial Permeability Transition Pore*
  • Mitochondrial Proteins / metabolism

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial Proteins
  • Calcium