Expression Regulation And Functional Analysis Of Mitochondria-localized Glutamic Acid Rich Protein (MGARP)

Mitochondrion is a very important organelle to cell. Its functions involvealmost every aspect of cell activities, including energy metabolism, apoptosis,cell cycle, calcium signaling, signal transduction and steroidogenesis.Mitochondria malfunction would result in many kinds of mitochondrialdiseases, such as diabetes, neurodegenerative diseases, etc.Mitochondrial-localized glutamic acidic rich protein (MGARP) is screened bymicro-array assay from mouse retinal cDNA library. It has a putativetrans-membrane domain and an unfolded C-terminus. It is highly expressed insteroidogenic tissue.In this research, we discovered that MGARP expression increases withmice development. It is highly expressed in adrenal gland and retina sincepostnatal day1while its expression in gonads emerges only after2-4weeksafter birth. MGARP expression is under the regulation ofhypothalamic-pituitary-gonadal (HPG) axis. MGARP expression in ovaries iscorrelated with sex hormones level during estrous cycle. Estrogen canregulate MGARP expression indirectly by a feedback and tissue-specificmechanism. GnRH can affect steroidogenesis through regulating HPG axis.Treatment with its antagonist can inhibit MGARP expression in mice gonads.Also, another HPG axis related hormone, leptin, can induce MGARPexpression in mice gonads and MGARP expression is significantlydown-regulated in granulosa cells of ovary in leptin knockout ob/ob mice. Wespeculates a mechanism that MGARP is get involved in steroidogenesis and isregulated by hormones derived from HPG axis in an extremely complicatedmanner.Besides, MGARP knockdown induces down-regulation of proliferativerate of Y1adrenal cell, changes of cell cycle, mitochondrial swelling and mitochondrial membrane potential loss, indicating an important role ofMGARP in maintaining normal mitochondrial function.In sum, our results imply that MGARP is an important protein for theproper function of mitochondria. It is highly probably get involved insteroidogenesis, development and reproduction. This work produces a solidfoundation for future reaserch of MGARP function and its mechanisms.