Deciphering the role of TOM complex components and understanding the ER Mitochondria crosstalk during mitochondrial proteotoxic stress

Abstract

In this doctoral work, in the first chapter (of the results section) we have shown the model generation of mitochondrial sub-compartment specific (IMS and matrix) proteotoxic stress in yeast Saccharomyces cerevisiae. We have used model misfolded proteins as stressor proteins and targeted it specifically to mitochondrial IMS and matrix. Furthermore, we have extensively characterized the phenotype of proteoxicity in mitochondrial IMS and matrix using various assays. In the second chapter, using systematic genetic interaction studies to validate the transcriptomics and proteomics data, we have revealed the specific modulatory role of mitochondrial TOM complex sub-units during mitochondrial IMS-specific proteotoxic stress. In the third chapter, by purifying the interactome of receptors of TOM complex components, Tom70 and Tom20, followed by its identification using mass-spectrometry, we revealed the changes in TOM-receptor interactome during mitochondrial proteotoxic stress. In the fourth chapter, we studied the ER-mitochondria cross-talk during mitochondrial stress. We deciphered the modulatory role of ER (Endoplasmic Reticulum) Unfolded Protein Response Pathway (UPR) in determining the cellular phenotype during mitochondrial proteotoxic stress.