Mitochondrial Dysfunction in C. elegans Activates Mitochondrial Relocalization and Nuclear Hormone Receptor-Dependent Detoxification Genes

Cell Metabolism
Kai MaoGary Ruvkun

Abstract

In Caenorhabditis elegans, mitochondrial dysfunction caused by mutation or toxins activates programs of detoxification and immune response. A genetic screen for mutations that constitutively induce C. elegans mitochondrial defense revealed reduction-of-function mutations in the mitochondrial chaperone hsp-6/mtHSP70 and gain-of-function mutations in the Mediator component mdt-15/MED15. The activation of detoxification and immune responses is transcriptionally mediated by mdt-15/MED15 and nuclear hormone receptor nhr-45. Mitochondrial dysfunction triggers redistribution of intestinal mitochondria, which requires the mitochondrial Rho GTPase miro-1 and its adaptor trak-1/TRAK1, but not nhr-45-regulated responses. Disabling the mdt-15/nhr-45 pathway renders animals more susceptible to a mitochondrial toxin or pathogenic Pseudomonas aeruginosa but paradoxically improves health and extends lifespan in animals with mitochondrial dysfunction caused by a mutation. Thus, some of the health deficits in mitochondrial disorders may be caused by the ineffective activation of detoxification and immune responses, which may be inhibited to improve health.

Citations

Sep 6, 2020·Molecular Genetics and Genomics : MGG·Jogender Singh
Oct 9, 2020·PLoS Pathogens·Sarah M Anderson, Read Pukkila-Worley
May 1, 2021·International Journal of Molecular Sciences·Chander K NegiLuděk Bláha
Sep 30, 2021·Life Science Alliance·Sonja K SooJeremy M Van Raamsdonk
Oct 9, 2021·Biochemical Society Transactions·Benjamin W Harding, Jonathan J Ewbank
Nov 10, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Joaquim Ferreira do Nascimento NetoWanderli Pedro Tadei

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