Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population

Mitochondrial function in aged hearts is impaired, and studies of isolated mitochondria are commonly used to assess their function. The two populations of cardiac mitochondria, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), are affected by aging. However, the yield of these mitochondria, particularly SSM, is limited in the mouse heart due to the smaller heart size. To address this issue, the authors developed a method to isolate a mixed population (MIX) of SSM and IFM mitochondria from a single mouse heart. The aim of the study was to compare the mitochondrial function between SSM, IFM, and the MIX population from young and aged mouse hearts. The MIX population had a higher yield of total protein and citrate synthase activity from both young and aged hearts compared to the individual yields of SSM or IFM. OXPHOS was decreased in aged SSM and IFM compared to young SSM and IFM, as well as in the MIX population isolated from aged hearts compared to young hearts, when using complex I or complex IV substrates. Furthermore, aging barely affected the sensitivity to MPTP opening in SSM, whereas the sensitivity was increased in IFM isolated from aged hearts and in the MIX population from aged hearts compared to the corresponding populations isolated from young hearts. These results suggest that mitochondrial dysfunction exists in aged hearts, and the isolation of a MIX population of mitochondria from the mouse heart is a potential approach to study mitochondrial function in the mouse heart.