Endoplasmic reticulum-mitochondria crosstalk: from junction to function across neurological disorders

Ann N Y Acad Sci. 2019 Dec;1457(1):41-60. doi: 10.1111/nyas.14212. Epub 2019 Aug 28.

Abstract

The endoplasmic reticulum (ER) and mitochondria are fundamental organelles highly interconnected with a specialized set of proteins in cells. ER-mitochondrial interconnections form specific microdomains, called mitochondria-associated ER membranes, that have been found to play important roles in calcium signaling and lipid homeostasis, and more recently in mitochondrial dynamics, inflammation, and autophagy. It is not surprising that perturbations in ER-mitochondria connections can result in the progression of disease, especially neurological disorders; hence, their architecture and regulation are crucial in determining the fate of cells and disease. The molecular identity of the specialized proteins regulating ER-mitochondrial crosstalk remains unclear. Our discussion here describes the physical and functional crosstalk between these two dynamic organelles and emphasizes the outcome of altered ER-mitochondrial interconnections in neurological disorders.

Keywords: Alzheimer's disease; ERMES; Huntington's disease; MAMs; Parkinson's disease; amyotrophic lateral sclerosis; cerebral ischemia.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Autophagy
  • Brain Ischemia / metabolism
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Line, Tumor
  • Disease Progression
  • Endoplasmic Reticulum / physiology*
  • Endoplasmic Reticulum Stress
  • GTP Phosphohydrolases / metabolism
  • Homeostasis
  • Humans
  • Huntington Disease / metabolism
  • Inflammation
  • Lipids / chemistry
  • Mice
  • Mitochondria / physiology*
  • Mitochondrial Dynamics
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Membranes / metabolism
  • Nervous System Diseases / physiopathology*
  • Parkinson Disease / metabolism
  • Presenilins / metabolism
  • Rats
  • Vesicular Transport Proteins / metabolism

Substances

  • Lipids
  • Mitochondrial Membrane Transport Proteins
  • PACS2 protein, human
  • Presenilins
  • Vesicular Transport Proteins
  • GTP Phosphohydrolases
  • Mfn1 protein, human
  • Calcium