title: HIF-1 regulates insect lifespan extension by inhibiting c-Myc-TFAM signaling and mitochondrial biogenesis.
abstract: Diapause (developmental arrest) is characterized by dramatic depression of metabolic activity and profoundly extends insect lifespan, similar to the Caenorhabditis elegans dauer stage and Drosophila longevity; however, the molecular mechanism of low metabolism in insect diapause is unclear. Here, we show that HIF-1α expression is significantly increased in diapause-destined pupal brains compared to nondiapause-destined pupal brains and that HIF-1α negatively regulates mitochondrial biogenesis. HIF-1α mediates this effect by inhibiting c-Myc activity via proteasome-dependent degradation of c-Myc. The mitochondrial transcription factor A (TFAM), which encodes a key factor involved in mitochondrial transcription and mitochondrial DNA replication, is activated by the binding of c-Myc to the TFAM promoter, thereby inducing transcription. Loss of TFAM expression is a major factor contributing to reducing the mitochondrial activity. Thus, the HIF-1α-c-Myc-TFAM signaling pathway participates in the regulation of mitochondrial activity for insect diapause or lifespan extension.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Xian-Wu
authors.initials: XW
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: JinHua
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China. Electronic address: xuweihua@mail.sysu.edu.cn.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Xu
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009036:Moths / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D001678:Organelle Biogenesis; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011679:Pupa / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019476:Insect Proteins; D024101:Mitochondrial Proteins; D016271:Proto-Oncogene Proteins c-myc; D046988:Proteasome Endopeptidase Complex
keywords: C-Myc; Developmental arrest; HIF-1α; Helicoverpa armigera; Lifespan extension; TFAM