Related Experiment Videos
Interfibrillar cardiac mitochondrial comples III defects in the aging rat heart
Charles L Hoppel1, Shadi Moghaddas, Edward J Lesnefsky
1Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. clh5@po.cwru.edu
Abstract:
We used the Fischer 344 rat as a model for aging effects on the heart. Cardiac interfibrillar mitochondria (IFM), located between the myofibrils, exhibit a decrease in protein yield and oxidative phosphorylation through complex III and IV in elderly (24 months) compared to adult controls (6 months). In contrast, subsarcolemmal mitochondria (SSM) located beneath the plasma membrane remained unchanged. The activity of electron transport complex III decreased only in the IFM with aging. Complex III and IV require an inner mitochondrial membrane lipid, cardiolipin for maximal activity. However, the content and composition of cardiolipin was unchanged in the IFM from aging hearts. We observed electron leakage in complex III at the myxothiazol site in the aging IFM accompanied by increased superoxide production. The aging heart sustains greater injury during ischemia and reperfusion compared to adult hearts. We propose that ischemic damage combines with aging defects in complex III to increase oxidative injury in aging hearts. Ischemia damaged complex III in both SSM and IFM from adult and aging hearts via impairment of the iron-sulfur subunit without the loss of the apoprotein. Thus, at the onset of reperfusion, complex III in IFM contains two defects in electron flow, which are likely to prime complex III for enhanced oxidant production during reperfusion, leading to increased damage in aging hearts.
Insights
Aging hearts show reduced mitochondrial function in interfibrillar mitochondria (IFM), leading to increased oxidative stress and injury during reperfusion. Subsarcolemmal mitochondria (SSM) function remained unaffected by aging.
Area of Science:
- Cardiovascular biology
- Mitochondrial function
- Aging research
Background:
- Aging impacts cardiac function, with mitochondria playing a key role.
- Mitochondria are categorized into subsarcolemmal (SSM) and interfibrillar (IFM) populations, potentially having distinct aging responses.
- Cardiac ischemia-reperfusion injury is exacerbated in aged hearts.
Purpose of the Study:
- To investigate age-related changes in cardiac mitochondrial function, specifically oxidative phosphorylation.
- To compare the effects of aging on interfibrillar mitochondria (IFM) versus subsarcolemmal mitochondria (SSM).
- To elucidate the mechanisms underlying increased cardiac injury during ischemia-reperfusion in aging hearts.
Main Methods:
- Utilized Fischer 344 rats at different ages (6 vs. 24 months) as an aging model.
- Isolated cardiac mitochondria (IFM and SSM) for assessment of protein yield and oxidative phosphorylation.
- Analyzed electron transport chain complex activity, cardiolipin content, and superoxide production.
Main Results:
- Elderly rats exhibited decreased protein yield and impaired oxidative phosphorylation (complex III and IV) in cardiac IFM, but not SSM.
- Aging specifically reduced electron transport complex III activity in IFM.
- Increased superoxide production and electron leakage at complex III were observed in aging IFM, despite unchanged cardiolipin levels.
Conclusions:
- Aging selectively impairs cardiac interfibrillar mitochondria (IFM) function, particularly electron transport complex III.
- Combined aging-related defects in IFM complex III and ischemia-reperfusion injury exacerbate oxidative damage in aging hearts.
- Defects in IFM complex III, exacerbated by ischemia, prime mitochondria for enhanced oxidant production during reperfusion, increasing cardiac injury.