Electron transport chain biogenesis activated by a JNK-insulin-Myc relay primes mitochondrial inheritance in Drosophila

• Published in: eLife 2019-10, Vol.8
• Main Authors: Wang, Zong-Heng, Liu, Yi, Chaitankar, Vijender, Pirooznia, Mehdi, Xu, Hong
• Format: Article
• Language: English
• Subjects: Animals; Biosynthesis; c-Jun N-terminal kinases; Cell growth; Copy number; Cysts; Developmental Biology; DNA-Binding Proteins - metabolism; Drosophila; Drosophila Proteins - metabolism; Eggs; Electron transport; Electron transport chain; Electron Transport Chain Complex Proteins - biosynthesis; Evolution; Extrachromosomal inheritance; Gene expression; Genes, Mitochondrial; Genetic aspects; Genomes; Germ cells; Glycerol; Insects; Insulin; Insulin - metabolism; insulin signaling; JNK signaling; MAP Kinase Kinase 4 - metabolism; Menopause; Metabolism; Mitochondria; Mitochondria - enzymology; Mitochondria - metabolism; Mitochondrial biogenesis; Mitochondrial DNA; Mitochondrial inheritance; mtDNA; Mutation; Myc; Myc protein; Oogenesis; Organelle Biogenesis; Phosphorylation; Physiological aspects; Proteins; Receptor Protein-Tyrosine Kinases - metabolism; Replication; Respiration; Signal Transduction; Stem cells; Transcription Factors - metabolism; Zoological research
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.49309

Oogenesis features an enormous increase in mitochondrial mass and mtDNA copy number, which are required to furnish mature eggs with an adequate supply of mitochondria and to curb the transmission of deleterious mtDNA variants. Quiescent in dividing germ cells, mtDNA replication initiates upon oocyte determination in the ovary, which necessitates active mitochondrial respiration. However, the underlying mechanism for this dynamic regulation remains unclear. Here, we show that an feedforward insulin-Myc loop promotes mitochondrial respiration and biogenesis by boosting the expression of electron transport chain subunits and of factors essential for mtDNA replication and expression, and for the import of mitochondrial proteins. We further reveal that transient activation of JNK enhances the expression of the insulin receptor and initiates the insulin-Myc signaling loop. This signaling relay promotes mitochondrial biogenesis in the ovary, and thereby plays a role in limiting the transmission of deleterious mtDNA mutations. Our study demonstrates cellular mechanisms that couple mitochondrial biogenesis and inheritance with oocyte development.