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Cyclophilin‐D is dispensable for mitochondrial apoptotic signaling through opening of the permeability transition pore in denervated muscle
Author(s) -
Godin Richard,
Daussin Frédéric N,
Ascah Alexis,
Deschênes Sonia,
Burelle Yan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1051.18
Subject(s) - mitochondrial permeability transition pore , denervation , microbiology and biotechnology , skeletal muscle , mitochondrion , apoptosis , myocyte , muscle atrophy , biology , mptp , chemistry , medicine , endocrinology , programmed cell death , biochemistry , dopaminergic , dopamine
We specifically determined whether the regulating protein cyclophilin‐D (CypD), through opening of the permeability transition pore (PTP), is involved in the activation of mitochondria‐derived apoptotic signaling previously described in skeletal muscle following loss of innervation. CypD‐defficient mice (CypD‐KO) and their littermate controls were submitted to unilateral sciatic nerve transection. Mitochondrial resistance to Ca2+‐induced opening of the PTP, and muscle apoptotic signaling were investigated 14 days post‐surgery. At the whole muscle level, lack of CypD, despite conferring greater resistance to PTP opening, did not protect against atrophy, release of mitochondrial pro‐apoptotic factors and activation of caspases following denervation. Denervation in CypD‐KO mice still resulted in a facilitation of PTP opening compared to normally innervated contralateral muscle. This indicates that CypD‐independent factors could poise mitochondria from denervated muscle toward PTP opening in vitro. All together, these results provide direct evidence that Cyp‐D‐dependent PTP opening is dispensable for apoptotic signaling in skeletal muscle following denervation.