The Department Mitochondrial Proteostasis investigates the role of mitochondria in ageing and age-associated diseases, such as cardiomyopathies, neurodegenerative diseases and cancer. The research focuses on mitochondrial dynamics and the functional plasticity of mitochondria, which allows metabolic adaptation and ensures cell survival in response to stress and physiological cues. We study how mitochondrial deficiency in ageing and disease triggers cellular stress responses, how these responses reshape the mitochondrial proteome, rewire the cellular metabolism, and protect against cell death, and how changes in the mitochondrial metabolic function are coupled to changes in mitochondrial shape.

We are investigating the molecular mechanisms that govern mitochondrial plasticity and heterogeneity in mice and in cultured cells, using a variety of proteomic approaches, combined with metabolomics and genome-wide CRISPR screens. We have observed a strong relationship between mitochondrial proteostasis, the cellular nucleotide metabolism and inflammation. Although observed in cultured senescent cells and in aged tissues, the contribution of mitochondria-dependent innate immune signaling to senescence and chronic inflammation in vivo remains poorly defined. In addition, we are interested in the cell- and tissue-specific heterogeneity of mitochondria within cells, between different cells within a given tissue, and between different tissues. Although mitochondrial heterogeneity is well established, it is not understood how it can be maintained within a cell and to which extent it contributes to the cell- and tissue-specific consequences of mitochondrial deficiency in ageing and disease. There are many exciting questions to be explored!