Mitochondrial calpains: Who, What, Where, When and Why?

James W. Geddes

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

2 Scopus citations


Evidence accumulated over the past two decades has clearly demonstrated that one or more calpains are localized to mitochondria. This evidence includes mitochondrial calpain activity, immunoreactivity, purifi cation, and N-terminal sequencing. Supporting data is greatest for CAPN1 and CAPN10, although the support for mitochondrial CAPN2 is also compelling. The mitochondrial localization of calpains may protect them from CAST inhibition, and also expose the proteases to Ca 2+ transients during mitochondrial Ca 2+ accumulation and/or opening of the mitochondrial permeability transition pore. One suggestion is that calpain activation may be required for mitochondrial permeability transition, with much stronger evidence demonstrating calpain activation in the aftermath of permeability transition pore opening. Several putative substrates of mitochondrial calpains have been identifi ed, with the greatest attention paid to apoptosis inducing factor. Although much data are consistent with the involvement of mitochondrial CAPN1 activation in the processing and release of apoptosis inducing factor, there are also contrasting data. All mitochondrial calpains identifi ed to date are also present in the cytosol, making selective mitochondrial inhibition or knockdown diffi cult and complicating analysis of mitochondrial calpains. Calpains are clearly present in mitochondria, much work remains to identify their substrates and physiological and pathological roles.

Original languageEnglish
Title of host publicationProteases in Health and Disease
Number of pages12
ISBN (Electronic)9781461492337
StatePublished - Jan 1 2013

Bibliographical note

Publisher Copyright:
© Springer Science+Business Media New York 2013. All rights are reserved.


  • Apoptosis
  • Apoptosis inducing factor
  • Calcium
  • Cell Death
  • Necrosis

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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