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Mitochondrial non‐heme iron levels determine susceptibility to permeability transition pore (PTP) with age: The effects of life‐long calorie restriction.
Author(s) -
Seo Arnold Young,
Xu Jinze,
Servais Stephane,
Hofer Tim,
Leeuwenburgh Christiaan
Publication year - 2008
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.22.2_supplement.142
Subject(s) - mitochondrion , calorie restriction , mitochondrial permeability transition pore , chemistry , calcium , heme , medicine , endocrinology , apoptosis , biochemistry , biology , programmed cell death , enzyme
Effects of life‐long calorie restriction (CR) on age associated changes in mitochondrial non‐heme iron (Fe) levels and PTP opening (calcium retention capacity of isolated mitochondria) were investigated in male Fischer 344 x Brown Norway rats. We isolated subsarcolemmal (SSM) and intermyofibrillar (IFM) mitochondria from quadriceps of ad libitium (AL) fed and 40% CR rats at 8, 18, 29 and 37 months of age. Fe content in both SSM and IFM increased with age with the greatest increases after 29‐months of age. Moreover, Fe content was greater in SSM as compared to IFM in all age groups. Importantly, PTP opening occurred sooner (less amounts of calcium additions) in the mitochondria with the highest Fe content (i.e., SSM). Furthermore, there was a significant negative correlation between PTP opening and the Fe level in the SSM and IFM of the AL rats. Strikingly, CR significantly attenuated the age‐associated Fe increase in the IFM and ameliorated the declined calcium retention capacity of SSM in the 37‐month old rats. This data suggests that mitochondrial non‐heme Fe, a potential strong pro‐oxidant, accumulates in the mitochondria with age and significantly affects calcium handling ability. In contrast, CR ‐an intervention known to extend mean and maximum life span‐ can attenuate mitochondrial‐mediated susceptibility to apoptosis. This research was supported by a grant to CL (AG17994 and AG21042), a grant to AYS (0615256B) and the Claude D. Pepper Older Americans Independence Center NIH Grant (1 P30 AG028740).