Mitochondria are multifunctional organelles. Thus, the formation of mitochondria is vital for cellular function in eukaryotes. Mitochondria comprise ~ 1500 cellular proteins, which are synthesized in the cytosol.
Mitochondrial biogenesis relies on efficient protein import as most mitochondrial proteins are imported via protein import pathways after synthesis in the cytosol. The mitochondrial intermembrane space (IMS) assembly (MIA) pathway that specifically imports proteins into the IMS is unique in that oxidative folding drives import and folding of target proteins. Specifically, a series of well-studied thiol-disulfide exchange reactions carried out by the two main components of the MIA pathway, namely Erv1 and Mia40 dictate vectorial translocation into the mitochondrial IMS. Studies have shown that several non-classical substrates, which do not possess the twin CX3C or CX9C motifs, utilize this pathway and importantly, connect the MIA pathway with other vital processes in the IMS, unrelated to oxidative folding. Hence, the MIA pathway is highly relevant in pathology of a spectrum of diseases such as, myopathies, neuropathies, Huntington’s disease, ALS and cancer. However, several unanswered questions remain. With the growing spectrum of substrates of this pathway, there is a need to understand the underlying molecular mechanisms. The MIA pathway must adapt to redox changes via interactions with antioxidant enzymes involved in reductive reactions in the IMS (thioredoxin 1, peroxiredoxin, and glutaredoxin2). However, no interactions of redox balancing systems in the IMS with the MIA machinery have been reported. Finally, because MIA pathway is operational under anaerobic conditions, there must be additional electron acceptors. The Dabir laboratory’s research is focused on identifying new electron acceptors/substrates that may modulate the MIA pathway.The lab currently has two major ongoing projects centered on different aspects of redox regulation of the MIA pathway. Because this import pathway is conserved in mammals, our studies in yeast can be applied to mammalian systems.
UNDERGRADUATE RESEARCH INTERNSHIP
If you are a LMU undergraduate interested in a research internship in the lab, please note that the minimum requirements are insatiable curiosity, unbridled enthusiasm, dependability, availability to work at least 4-6 hours per week during the academic year and a commitment to 12 months or more in the lab, including the summer. This is what it takes for a meaningful research and training experience. Prior lab experience of any kind (Biology labs, stockroom work, research in another lab etc) is a plus. If you are interested in applying, please fill out the online form.