Metabolism is firmly defined by the mitochondria. They dictate the bioenergetic capacity of our cells and provide us with critical metabolites. The bulk of cellular energy is generated by the elaborative molecular machines embedded inside the mitochondrial membranes, jointly known as the OXPHOS system. The everyday stress impacts the composition and functionality of OXPHOS, leading to its dysfunction. Consequently, compromised OXPHOS fitness has been implicated in a broad spectrum of disorders, including cancer, diabetes, obesity, ischemia-reperfusion injury, neurodegeneration, or aging.

What are the mechanisms that sculpture OXPHOS in response to challenges? Is there a way to repair it when injured by stress? We recently started to recognize that mitochondrial bioenergetics stays under the constant surveillance of dedicated proteostatic machinery. Yet, the exact mechanisms and responsible players remain mostly elusive.

Our research aims to dissect the mechanisms that mediate the quality control of OXPHOS exposed to disease-associated conditions and trace the molecular signals that steer its degradation. With the help of modern proteomics and advanced biochemical and molecular biology approaches, we discover the damage hot-spots in mammalian mitochondria and identify the factors responsible for their recognition and repair.

Our findings will help to understand how metabolic quality control contributes to the known cellular stress-responses. Furthermore, OXPHOS salvage can constitute an attractive target for novel therapies against a broad range of human diseases.