Mitochondrial Cyclosporine A-Independent Palmitate/Ca2+-Induced Permeability Transition Pore (PA-mPT Pore) and Its Role in Mitochondrial Function and Protection against Calcium Overload and Glutamate Toxicity

Cells. 2021 Jan 11;10(1):125. doi: 10.3390/cells10010125.

Abstract

A sharp increase in the permeability of the mitochondrial inner membrane known as mitochondrial permeability transition (or mPT) occurs in mitochondria under the conditions of Ca2+ and ROS stress. Permeability transition can proceed through several mechanisms. The most common mechanism of mPT is based on the opening of a cyclosporine A (CSA)-sensitive protein channel in the inner membrane. In addition to the CSA-sensitive pathway, mPT can occur through the transient opening of lipid pores, emerging in the process of formation of palmitate/Ca2+ complexes. This pathway is independent of CSA and likely plays a protective role against Ca2+ and ROS toxicity. The review considers molecular mechanisms of formation and regulation of the palmitate/Ca2+-induced pores, which we designate as PA-mPT to distinguish it from the classical CSA-sensitive mPT. In the paper, we discuss conditions of its opening in the biological membranes, as well as its role in the physiological and pathophysiological processes. Additionally, we summarize data that indicate the involvement of PA-mPT in the protection of mitochondria against calcium overload and glutamate-induced degradation in neurons.

Keywords: calcium overload; glutamate toxicity; mitochondria; palmitate/Ca2+-induced permeability transition pore; palmitic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cyclosporine / metabolism*
  • Glutamic Acid / toxicity*
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Permeability Transition Pore / metabolism*
  • Palmitates / metabolism*

Substances

  • Mitochondrial Permeability Transition Pore
  • Palmitates
  • Glutamic Acid
  • Cyclosporine
  • Calcium