Mitochondria associated ER membranes and cerebral ischemia: Molecular mechanisms and therapeutic strategies

Pharmacol Res. 2023 May:191:106761. doi: 10.1016/j.phrs.2023.106761. Epub 2023 Apr 5.

Abstract

Endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in mammalian cells. The physical connection between them is mitochondria associated ER membranes (MAM). In recent years, studies on endoplasmic reticulum and mitochondria have shifted from independent division to association and comparison, especially MAM has gradually become a research hotspot. MAM connects the two organelles, not only to maintain their independent structure and function, but also to promote metabolism and signal transduction between them. This paper reviews the morphological structure and protein localization of MAM, and briefly analyzes the functions of MAM in regulating Ca2+ transport, lipid synthesis, mitochondrial fusion and fission, endoplasmic reticulum stress and oxidative stress, autophagy and inflammation. Since ER stress and mitochondrial dysfunction are important pathological events in neurological diseases including ischemic stroke, MAM is likely to play an important role in cerebral ischemia by regulating the signaling of the two organelles and the crosstalk of the two pathological events.

Keywords: Autophagy; Ca(2+); Cerebral ischemia; Mitochondria associated ER membranes (MAM).

Publication types

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

MeSH terms

  • Animals
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Mammals
  • Mitochondria / metabolism
  • Mitochondrial Membranes* / metabolism
  • Signal Transduction