Delineation Of The Role Of Emr1 In Regulating The Contact Between Mitochondria And The Endoplasmic Reticulum

The organelles in eukaryotic cells continuously communicate to exchange cellular materials like proteins,lipids,and metabolites.The vesicular transport system is generally used for the exchange of these materials.Mitochondria rely on membrane contact sites,not the vesicular system,to exchange cellular materials.Several contact sites between mitochondria and the ER,vacuole,and peroxisomes have been discovered.The endoplasmic reticulum mitochondria encounter structure(ERMES)complex is a tethering complex that establishes a membrane contact site between the ER and mitochondria.The ERMES complex plays important roles in mtDNA inheritance,mitochondrial fission and segregation,lipid transfer,and mitophagy.Recent findings highlight that the ERMES complex is dynamic and that the size of the ERMES varies according to genetic and environmental cues.Therefore,the regulation of the ERMES complex has been a matter of interest among many groups.This dissertation reports an uncharacterized mitochondrial membrane protein,Emrl,from the fission yeast Schizosaccharomyces pombe.The absence of Emr1 significantly alters the size and number of ERMES foci.In cells lacking Emr1,the size of ERMES foci increases but the number of ERMES foci decreases.Emr1 colocalizes with the ERMES complex and physically interacts with Mdm12,the core component of the ERMES complex.Like ERMES mutants,the cells lacking Emr1 show defective mitochondrial morphologies and mitochondrial segregation.The impairment of the ERMES complex leads to compromised contact between the ER and mitochondria.Interestingly,the synthetic protein ChiMERA capable of tethering the ER to mitochondria can rescue the mitochondrial abnormality in the cells lacking Emr1.By contrast,ChiMERA cannot restore normal ERMES assembly in cells lacking Emrl,highlighting the important role of Emr1 in promoting ERMES formation.Moreover,I demonstrated that the Cterminus of Emrl,exposed to the cytoplasm,is essential for the proper ERMES assembly.Hence,I have identified a new regulator of the ERMES complex and have demonstrated the role of Emr1 in regulating the ERMES complex.This work paves the way for the further understanding of the underlying mechanisms of the ER-mitochondria contact.