Inactivation of cardiolipin synthase triggers changes in mitochondrial morphology

FEBS Lett. 2018 Jan;592(2):209-218. doi: 10.1002/1873-3468.12948. Epub 2017 Dec 27.

Abstract

Mitochondrial tubular structures are maintained by a balance between membrane fusion and fission that is regulated by various factors, including Drp1 and mitofusin/fzo-1. Here we report the role of cardiolipin (CL) synthase in the regulation of mitochondrial morphology. Knockdown of CL synthase induced mitochondrial elongation in nematode and human cells. Knockdown of both nematode cardiolipin synthase and drp-1 or fzo-1 suggested that knocking down CL synthase decreases mitochondrial division. Mass spectrometric analysis of human CL synthase-knocked down cells revealed a decreased amount of CL and an accumulation of phosphatidylglycerol, a CL precursor. Knockdown of other genes involved in CL synthesis did not influence mitochondrial morphology. Thus, mitochondrial elongation may result from the accumulation of phosphatidylglycerol rather than decreased CL.

Keywords: CRLS1; cardiolipin; mitochondrial morphology; phosphatidylglycerol.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics*
  • Cardiolipins / metabolism
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Mass Spectrometry
  • Membrane Proteins / genetics*
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics
  • Mitochondrial Proteins / genetics*
  • Muscle Cells / metabolism
  • Phosphatidylglycerols / metabolism
  • Transferases (Other Substituted Phosphate Groups) / genetics*

Substances

  • CRLS1 protein, human
  • Caenorhabditis elegans Proteins
  • Cardiolipins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Phosphatidylglycerols
  • Transferases (Other Substituted Phosphate Groups)
  • CRLS-1 protein, C elegans