title: Transcriptional response to mitochondrial protease IMMP2L knockdown in human primary astrocytes.
abstract: IMMP2L encodes the inner membrane peptidase subunit 2, a mitochondrial protease involved in cleaving the space-sorting signals of mitochondrial membrane proteins. IMMP2L has been implicated in Tourette syndrome, but how its dysfunction contributes to the neurodevelopmental phenotype remains unclear. Here we show that IMMP2L transcription requires Topoisomerase I in human primary astrocytes, and characterize the downstream effects of IMMP2L knockdown on gene expression. We demonstrate that IMMP2L knockdown leads to dysregulation of genes involved in central nervous system development. We also find that the transcriptional response to IMMP2L knockdown partially overlaps the one induced by mitochondrial complex III inhibition. Overall, these data bring further insight into the molecular consequences of IMMP2L dysfunction in the brain.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Akira
authors.initials: A
authors.lastname: Gokoolparsadh
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Fang
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Peijie
authors.initials: P
authors.lastname: Lin
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pardy
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Valsamma
authors.initials: V
authors.lastname: Eapen
authors.affiliation: University of Western Sydney, Sydney, Australia.
authors.forename: Raymond
authors.initials: R
authors.lastname: Clarke
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia. Electronic address: i.voineagu@unsw.edu.au.
authors.forename: Irina
authors.initials: I
authors.lastname: Voineagu
mesh_terms: D000968:Antimycin A / Q000737:chemistry; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D005879:Tourette Syndrome / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D000968:Antimycin A; D010450:Endopeptidases; C425070:IMMP2L protein, human; D004264:DNA Topoisomerases, Type I; D014450:Electron Transport Complex III
keywords: Human primary astrocytes; IMMP2L; Mitochondria; Retrograde signaling; Tourette syndrome; Transcription