Mitochondrial iron accumulation with age and functional consequences.
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 x 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.
Seo
Arnold Y
AY
Department of Aging and Geriatrics, Division of Biology of Aging, Genomics and Biomarkers Core of the Institute on Aging, University of Florida, Gainesville, FL 32611, USA.
Xu
Jinze
J
Servais
Stephane
S
Hofer
Tim
T
Marzetti
Emanuele
E
Wohlgemuth
Stephanie E
SE
Knutson
Mitchell D
MD
Chung
Hae Young
HY
Leeuwenburgh
Christiaan
C
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D007501:Iron / Q000009:adverse effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D008930:Mitochondria, Liver / Q000502:physiology; D008931:Mitochondria, Muscle / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D010084:Oxidation-Reduction; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D007501:Iron; D002118:Calcium