Open AccessCyclophilin D links programmed cell death and organismal aging in Podospora anserina
Author(s) -
Brust Diana,
Daum Bertram,
Breunig Christine,
Hamann Andrea,
Kühlbrandt Werner,
Osiewacz Heinz D.
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00609.x
Subject(s) - podospora anserina , cyclophilin , biology , programmed cell death , mitochondrial permeability transition pore , peptidylprolyl isomerase , cis trans isomerases , mitochondrion , microbiology and biotechnology , oxidative stress , genetics , apoptosis , biochemistry , isomerase , mutant , gene
Summary Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl‐ cis,trans ‐isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina . Here, we show that treatment of the P. anserina wild‐type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild‐type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging.