Open AccessMitochondrial iron accumulation with age and functional consequences
Author(s) -
Seo Arnold Y. ,
Xu Jinze ,
Servais Stephane ,
Hofer Tim ,
Marzetti Emanuele ,
Wohlgemuth Stephanie E. ,
Knutson Mitchell D. ,
Chung Hae Young ,
Leeuwenburgh Christiaan
Publication year - 2008
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.1474-9726.2008.00418.x
Subject(s) - mitochondrion , mitochondrial permeability transition pore , biology , mptp , oxidative phosphorylation , skeletal muscle , oxidative stress , heme , microbiology and biotechnology , medicine , endocrinology , apoptosis , biochemistry , programmed cell death , dopaminergic , dopamine , enzyme
Summary During the aging process, an accumulation of non‐heme iron disrupts cellular homeostasis and contributes to the mitochondrial dysfunction typical of various neuromuscular degenerative diseases. Few studies have investigated the effects of iron accumulation on mitochondrial integrity and function in skeletal muscle and liver tissue. Thus, we isolated liver mitochondria (LM), as well as quadriceps‐derived subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), from male Fischer 344× Brown Norway rats at 8, 18, 29 and 37 months of age. Non‐heme iron content in SSM, IFM and LM was significantly higher with age, reaching a maximum at 37 months of age. The mitochondrial permeability transition pore (mPTP) was more susceptible to the opening in aged mitochondria containing high levels of iron (i.e. SSM and LM) compared to IFM. Furthermore, mitochondrial RNA oxidation increased significantly with age in SSM and LM, but not in IFM. Levels of mitochondrial RNA oxidation in SSM and LM correlated positively with levels of mitochondrial iron, whereas a significant negative correlation was observed between the maximum Ca 2+ amounts needed to induce mPTP opening and iron contents in SSM, IFM and LM. Overall, our data suggest that age‐dependent accumulation of mitochondrial iron may increase mitochondrial dysfunction and oxidative damage, thereby enhancing the susceptibility to apoptosis.