Regulation of autophagy by mitochondrial phospholipids in health and diseases

Paul Hsu, Yuguang Shi

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

Abstract

Autophagy is an evolutionarily conserved mechanism that maintains nutrient homeostasis by degrading protein aggregates and damaged organelles. Autophagy is reduced in aging, which is implicated in the pathogenesis of aging-related diseases, including cancers, obesity, type 2 diabetes, cardiovascular diseases, and neurodegenerative diseases. Mitochondria-derived phospholipids cardiolipin, phosphatidylethanolamine, and phosphatidylglycerol are critical throughout the autophagic process, from initiation and phagophore formation to elongation and fusion with endolysosomal vesicles. Cardiolipin is also required for mitochondrial fusion and fission, an important step in isolating dysfunctional mitochondria for mitophagy. Furthermore, genetic screen in yeast has identified a surprising role for cardiolipin in regulating lysosomal function. Phosphatidylethanolamine plays a pivotal role in supporting the autophagic process, including autophagosome elongation as part of lipidated Atg8/LC3. An emerging role for phosphatidylglycerol in AMPK and mTORC1 signaling as well as mitochondrial fission may provide the first glimpse into the function of phosphatidylglycerol apart from being a precursor for cardiolipin. This review examines the effects of manipulating phospholipids on autophagy and mitophagy in health and diseases, as well as current limitations in the field. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.

Original languageEnglish (US)
Pages (from-to)114-129
Number of pages16
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1862
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Autophagy
  • Cardiolipin
  • Mitophagy
  • Phosphatidylethanolamine
  • Phosphatidylglycerol

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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