Divergences in the Control of Mitochondrial Respiration Are Associated With Life-Span Variation in Marine Bivalves

The role played by mitochondrial function in the aging process has been a subject of intense debate in the past few decades, as part of the efforts to understand the mechanistic basis of longevity. The mitochondrial oxidative stress theory of aging suggests that a progressive decay of this organelle's function leads to an exacerbation of oxidative stress, with a deleterious impact on mitochondrial structure and DNA, ultimately promoting aging. Among the traits suspected to be associated with longevity is the variation in the regulation of oxidative phosphorylation, potentially affecting the management of oxidative stress. Longitudinal studies using the framework of metabolic control analysis have shown age-related differences in the flux control of respiration, but this approach has seldom been taken on a comparative scale. Using 4 species of marine bivalves exhibiting a large range of maximum life span (from 28 years to 507 years), we report life-span-related differences in flux control at different steps of the electron transfer system. Increased longevity was characterized by a lower control by NADH (complex I-linked) and Succinate (complex II-linked) pathways, while respiration was strongly controlled by complex IV when compared to shorter-lived species. Complex III exerted strong control over respiration in all species. Furthermore, high longevity was associated with higher citrate synthase activity and lower ATP synthase activity. Relieving the control exerted by the electron entry pathways could be advantageous for reaching higher longevity, leading to increased control by complex IV, the final electron acceptor in the electron transfer system.