Regulation of mitochondrial plasticity by the i-AAA protease YME1L

Yohsuke Ohba, Thomas MacVicar, Thomas Langer

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)

Abstract

Mitochondria are multifaceted metabolic organelles and adapt dynamically to various developmental transitions and environmental challenges. The metabolic flexibility of mitochondria is provided by alterations in the mitochondrial proteome and is tightly coupled to changes in the shape of mitochondria. Mitochondrial proteases are emerging as important posttranslational regulators of mitochondrial plasticity. The i-AAA protease YME1L, an ATP-dependent proteolytic complex in the mitochondrial inner membrane, coordinates mitochondrial biogenesis and dynamics with the metabolic output of mitochondria. mTORC1-dependent lipid signaling drives proteolytic rewiring of mitochondria by YME1L. While the tissue-specific loss of YME1L in mice is associated with heart failure, disturbed eye development, and axonal degeneration in the spinal cord, YME1L activity supports growth of pancreatic ductal adenocarcinoma cells. YME1L thus represents a key regulatory protease determining mitochondrial plasticity and metabolic reprogramming and is emerging as a promising therapeutic target.

Original languageEnglish
Pages (from-to)877-890
Number of pages14
JournalBiological Chemistry
Volume401
Issue number6-7
DOIs
Publication statusPublished - 2020 May 26
Externally publishedYes

Keywords

  • i-AAA protease
  • cancer
  • LIPIN1
  • mitochondria
  • mitochondrial plasticity
  • mitochondrial proteases
  • mTORC1
  • YME1L

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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