My project aims to explore novel roles of the mitochondrial processing peptidase beyond its well-known function of cleaving mitochondrial targeting sequences. Mitochondria are multifaced organelles that regulate energy metabolism, apoptosis, immunity and other cellular processes. Despite having their own genome, most mitochondrial proteins are nuclear-encoded, synthesized in the cytosol, and enter mitochondria via N-terminal mitochondrial targeting sequences (MTSs). The mitochondrial processing peptidase (MPP) cleaves these MTSs in the mitochondrial matrix to enable proper protein folding and localization. While yeast MPP has been well characterized little is known about MPP’s function in vertebrates beyond this import-specific cleavage event. In addition, mutations in MPP can cause different forms of ataxia or neurodegeneration during infancy. Recent proximity-based studies suggest that the MPP subunits may form distinct subcomplexes with other mitochondrial proteins. Over the course of this scholarship period, I aim to characterize these interactions through recombinant purification for structural determination and in vitro assays to assess the functional impact of these interactions. To complement this, we will investigate the proteomic consequences of perturbing these interactions in cells. Collectively, this research aims to redefine MPP’s role as a dynamic regulator of mitochondrial function beyond protein import and may offer insights into the molecular basis of diseases linked to mitochondrial dysfunction.

Danielle will hold the Scholarship and perform her research in the lab of Prof. Jean-François Trempe