Research Projects

In recent years, there has been a growing interest in mitochondrial biology and stress response pathways elicited by this unique organelle. Mitochondria are one of the cellular hotspots for proteotoxic stress or protein misfolding stress due to its extreme dependence on the nucleus, complex two-membrane architecture, different oxido-reductive environments, and differences in resident Protein Quality Control (PQC) machines of the two intra-mitochondrial sub-compartments, the Inter-Membrane space (IMs) and matrix. Mis-targeting of proteins to mitochondrial organelles like the ER and higher intra-mitochondrial temperature are major factors leading to protein misfolding problems leading to proteotoxicity in mitochondria. A recent study in yeast saccharomyces cerevisiae revealed that mitochondrial membrane-bound sub-compartments, IMs, and matrix are comparatively more vulnerable to proteotoxic stresses than other sub-cellular compartments. Molecular studies on yeast strains expressing misfolded proteins in the mitochondrial IMs or matrix revealed unique pathways differentially upregulated or downregulated due to stress. VMs1 was found to be upregulated in matrix stress, a component of the Mitochondria Associated Degradation (MAD) pathway. Deletion of VMs1 leads to an enhancement of the toxic phenotype of strains expressing misfolded proteins in the mitochondrial matrix, indicating an important role of the protein in stress response pathways elicited due to matrix proteotoxic stress. Overexpression of VMs1 was found to be extremely detrimental during mitochondrial proteotoxic stress, as the toxicity was aggravated upon overexpression. These findings have prompted further exploration of the modulatory role of this protein during mitochondrial proteotoxic stress.