MITOMAR · The mitochondrial mono-ADP-ribosylation landscape

Metabolism sustains life, providing the right amount of energy to keep the body active and responsive to a changing environment. Abnormal metabolism is at the heart of many health problems, including cancer, neurodegenerative disorders and diabetes, which severely affect an individual’s quality of life and have become high priorities for Europe. Our understanding of the mechanisms that underlie these diseases has rapidly evolved over recent years. Yet, the development of novel, effective interventions still requires the further identification and analysis of mechanistically ill-understood, but physiologically important molecular mechanisms and signaling networks.The MitoMAR project dissects mitochondrial mono-ADP-ribosylation, a highly dynamic, environment-responsive post-translational modification of cellular proteins, which links changes in mitochondrial function and NAD+ production to the aetiology of these diseases. We are studying the mitochondrial ADP-ribosyl-proteome under a variety of growth conditions and will describe the biological role of mitochondrial ADP-ribosylation for a subset of modified targets, characterizing their interaction with mitochondrial ADP-ribosyl polymerases and hydrolasesEvidence indicates that ADP-ribosylation biology underlies the pathomechanisms of cancer, neurodegenerative and metabolic disorders. The main aim of the MitoMAR project is to advance our understanding of the proteins and networks that are modulated by mitochondrial mono-ADP-ribosylation. Considering the central role of mitochondria and metabolism in human health, the expected results will be immediately useful to other researchers, and will ultimately facilitate the development of therapeutic approaches by identifying new drug targets.