Mitochondria in ageing: there is metabolism beyond the ROS.

Mitochondria are responsible for a series of metabolic functions. Superoxide leakage from the respiratory chain and the resulting cascade of reactive oxygen species-induced damage, as well as mitochondrial metabolism in programmed cell death, have been intensively studied during ageing in single-cellular and higher organisms. Changes in mitochondrial physiology and metabolism resulting in ROS are thus considered to be hallmarks of ageing. In this review, we address 'other' metabolic activities of mitochondria, carbon metabolism (the TCA cycle and related underground metabolism), the synthesis of Fe/S clusters and the metabolic consequences of mitophagy. These important mitochondrial activities are hitherto less well-studied in the context of cellular and organismic ageing. In budding yeast, they strongly influence replicative, chronological and hibernating lifespan, connecting the diverse ageing phenotypes studied in this single-cellular model organism. Moreover, there is evidence that similar processes equally contribute to ageing of higher organisms as well. In this scenario, increasing loss of metabolic integrity would be one driving force that contributes to the ageing process. Understanding mitochondrial metabolism may thus be required for achieving a unifying theory of eukaryotic ageing.