Priority Programme “Integration of mitochondria into the cellular proteostasis network” (SPP 2453)
Deadline: 31 Oktober 2023
In March 2023, the Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) established the Priority Programme “Integration of mitochondria into the cellular proteostasis network” (SPP 2453). The programme is designed to run for six years. The present call invites proposals for the first three-year funding period.
Mitochondrial functions and biogenesis depend on the import of more than 1000 proteins that are produced as precursors on cytosolic ribosomes. The vast majority of mitochondrial proteins are imported in a post-translational manner. After synthesis on ribosomes, molecular chaperones guide these proteins to the mitochondrial surface. Despite some progress in the last years, the mechanisms of protein targeting to mitochondria and its quality control are poorly understood. Recent studies have revealed that non-imported mitochondrial precursor proteins challenge the cytosolic proteostasis system, particularly in cells with defective mitochondrial functions, linking mitochondrial fitness to cellular viability. Conversely, perturbations of the proteostasis network can cause accumulation of mitochondrial precursor proteins and affect mitochondrial biogenesis. In this priority programme, we will combine the expertise from two different fields, mitochondrial protein import and cellular proteostasis, to allow the analysis of molecular mechanisms that govern targeting and quality control of mitochondrial precursor proteins. We will use and further develop advanced technologies to elucidate the interplay of mitochondrial biogenesis with cellular proteostasis using three defined model systems (Saccharomyces cerevisiae, cultured mammalian cells and Caenorhabditis elegans).
The overarching goal of this priority programme is to uncover the molecular principles of quality control mechanisms for the intracellular targeting of mitochondrial precursor proteins and their fate in case of ineffective targeting or import. Projects should address one of the following questions:
- What are the molecular mechanisms that ensure the reliable intracellular transport of precursor proteins to mitochondria?
- How do quality control factors of different cellular compartments cooperate to remove non-imported mitochondrial proteins?
- How do proteostasis network components such as chaperones or proteases support dynamic changes of the mitochondrial proteome upon adaption to specific cellular demands?
The priority programme will exclusively fund tandem projects combining one expert from the mitochondrial protein import field and one expert from the cellular proteostasis field. To maintain the focus on this priority programme, we do not aim to fund:
- Predominantly descriptive projects that lack a focus on molecular mechanisms.
- Research projects that are not directly related to mitochondrial precursor proteins, such as studies analysing mitophagy, apoptosis or antiviral signalling. The focus of the priority programme is centered on targeting and quality control of mitochondrial precursor proteins.