Bahhir 2019 PLoS Genet

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Bahhir D, Yalgin C, Ots L, Jaervinen S, George J, Naudi A, Krama T, Krams I, Tamm M, Andjelkovic A, Dufour E, Gonzalez de Cozar JM, Gerards M, Parhiala M, Pamplona R, Jacobs HT, Joers P (2019) Manipulating mtDNA in vivo reprograms metabolism via novel response mechanisms. PLoS Genet [Epub ahead of print].

» PMID: 31584940 Open Access

Bahhir D, Yalgin C, Ots L, Jaervinen S, George J, Naudi A, Krama T, Krams I, Tamm M, Andjelkovic A, Dufour E, Gonzalez de Cozar JM, Gerards M, Parhiala M, Pamplona R, Jacobs HT, Joers P (2019) PLoS Genet

Abstract: Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activity induced a type II diabetes-like phenotype involving deactivation of Akt kinase and inhibition of pyruvate dehydrogenase, whilst translocation decreased post-translational protein acetylation by cytonuclear depletion of acetyl-CoA (AcCoA). The associated decease in the concentrations of ketogenic amino acids also produced downstream effects on physiology and behavior, attributable to decreased neurotransmitter levels. We thus provide evidence for novel signaling pathways connecting mtDNA to metabolism, distinct from its role in supporting OXPHOS.


Bioblast editor: Plangger M O2k-Network Lab: FI Tampere Dufour E, FI Helsinki Jacobs HT


Labels: MiParea: mtDNA;mt-genetics 


Organism: Drosophila 

Preparation: Homogenate 


Coupling state: LEAK, OXPHOS  Pathway: N, Gp, CIV, ROX 


Labels, 2019-10