Macromolecular reorganizations in mitochondria during aging

As the powerhouse of the eukaryotic cell, the mitochondrion plays a major role in age-related processes. The respiratory chain constantly produces deleterious reactive oxygen species (ROS), which cause accumulating damage, and ultimately leads to cell death. We have performed electron cryo-tomography on whole mitochondria isolated from the ageing model organism Podospora anserina to investigate the macromolecular organization of the ATP synthase and respiratory chain complexes in young and old cells. In mitochondria isolated from young Podospora cells the mitochondrial ATP synthase forms extended dimer ribbons located along highly curved ridges of the mitochondrial cristae membrane, whereas respiratory supercomplexes are located in the flat membrane regions flanking them. During ageing we observe a dramatic change in the mitochondrial morphology, which is accompanied by a retraction of the cristae, fragmentation of the mitochondrial matrix, a loss of respiratory supercomplexes and a disassembly of ATP synthase dimer ribbons. Overexpression of the mitochondrial chaperone cyclophilin-D (PaCypD), which has been previously shown to be a key player in apoptotic pathways and to bind the ATP synthase, prematurely induces these mitochondrial transitions as well as cellular senescence. We suggest that the oligomeric state of the ATP synthase plays a key role in ageing related mitochondrial degradation processes and, consequently, apoptosis.