CaltechAUTHORS
Published June 3, 2009 | Version public
Journal Article Metadata-only

SLP-2 is required for stress-induced mitochondrial hyperfusion

Creators

  • 1. ROR icon University of Geneva
  • 2. ROR icon Dana-Farber Cancer Institute
  • 3. ROR icon University of Lorraine
  • 4. ROR icon University of California, San Diego
  • 5. ROR icon National Institute of Neurological Disorders and Stroke
  • 6. ROR icon University of Cologne
  • 7. ROR icon TU Darmstadt
  • 8. ROR icon California Institute of Technology
  • 9. ROR icon Max Delbrück Center for Molecular Medicine

Abstract

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.

Additional Information

© 2009 European Molecular Biology Organization. Received: 24 November 2008; accepted: 12 March 2009; published online: 9 April 2009. We thank Dr Mihara and Dr Ishihara for rat OPA1-V1, OPA1-V1DS1, OPA1-V7, and AIF-OPA1-V7230–997 cDNAs, Dr Scorrano for OPA1 cDNA, Dr Rojo for human Mfn1 cDNA, Professor Wiesner for 143B rho0 cells, Professor Picard for pdtTomato-C1, Dr Dencher and Dr Madrenas for support, Dr Rossignol for his advices and all members of the lab for fruitful discussions. This work was funded by the Deutsche Forschungsgemeinschaft (DFG) (TO540/1-1), the NIH intramural program, the Swiss National Science Foundation (subsidy 3100A0-109419/1), Oncosuisse Trust, Roche Research Foundation and the Geneva Department of Education. FK is funded in part by the European Union (MiMage, EC FP6 Contract No. LSHM-CT-2004-512020).

Additional details

Identifiers

PMCID
PMC2693158
Eprint ID
15560
DOI
10.1038/emboj.2009.89
Resolver ID
CaltechAUTHORS:20090903-083208055

Related works

Describes
10.1038/emboj.2009.89 (DOI)

Funding

Deutsche Forschungsgemeinschaft (DFG)
TO540/1-1
NIH
Swiss National Science Foundation
3100A0-109419/1
Oncosuisse Trust
Roche Reasearch Foundation
Geneva Department of Education
European Union
LSHM-CT-2004-512020

Dates

Created
2009-09-22
Created from EPrint's datestamp field
Updated
2021-11-08
Created from EPrint's last_modified field