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

The organelles in eukaryotic cells continuously communicate with each other for exchanging 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,but 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 one of the tethering complexes that establish 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 the size of the complex varies according to genetic and environmental cues.Therefore,the regulation of the ERMES complex has been a matter of interest among many groups.In this dissertation,I report an uncharacterized mitochondrial membrane protein,Emrl,from the fission yeast Schizosaccharomyces pombe.The absence of Emrl significantly alters the size and number of ERMES foci.In cells lacking Emrl,ERMES foci increase in size but decrease in number.Emrl co-localizes with the ERMES complex and has a physical interaction with Mdml2,the core component.of the ERMES complex.Similar to ERMES mutants,the cells lacking Emrl show defective mitochondrial morphologies and mitochondria segregation in the cells is impaired.The impairment of ERMES likely leads to compromised contact between the ER and mitochondria,and interestingly,the synthetic protein ChiMERA(a construct tethering the ER to mitochondria)is able to rescue the mitochondrial abnormality in the cells lacking Emr1.By contrast,ChiMERA is unable to restore normal ERMES assembly,highlighting the important role of Emrl in promoting ERMES formation.Moreover,we observed that the C-terminus of Emrl,which is exposed to the cytoplasm,is essential for the proper ERMES assembly.Hence,we 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.