SLP-2 is required for stress-induced mitochondrial hyperfusion

EMBO J. 2009 Jun 3;28(11):1589-600. doi: 10.1038/emboj.2009.89. Epub 2009 Apr 9.


Mitochondria are dynamic organelles, the morphology of which results from an equilibrium between two opposing processes, fusion and fission. Mitochondrial fusion relies on dynamin-related GTPases, the mitofusins (MFN1 and 2) in the outer mitochondrial membrane and OPA1 (optic atrophy 1) in the inner mitochondrial membrane. Apart from a role in the maintenance of mitochondrial DNA, little is known about the physiological role of mitochondrial fusion. Here we report that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses. This process precedes mitochondrial fission when it is triggered by apoptotic stimuli such as UV irradiation or actinomycin D. Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2. In the absence of SLP-2, L-OPA1 is lost and SIMH is prevented. SIMH is accompanied by increased mitochondrial ATP production and represents a novel adaptive pro-survival response against stress.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cells, Cultured
  • Dactinomycin / toxicity
  • Fibroblasts / drug effects
  • Fibroblasts / physiology*
  • Fibroblasts / radiation effects
  • GTP Phosphohydrolases / physiology
  • Membrane Proteins / physiology*
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mitochondria / radiation effects
  • Stress, Physiological*
  • Ultraviolet Rays


  • Membrane Proteins
  • Sytl2 protein, mouse
  • Dactinomycin
  • Adenosine Triphosphate
  • GTP Phosphohydrolases
  • Mfn1 protein, mouse
  • Opa1 protein, mouse