Perks 2017 Sci Adv

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Perks KL, Ferreira N, Richman TR, Ermer JA, Kuznetsova I, Shearwood AJ, Lee RG, Viola HM, Johnstone VPA, Matthews V, Hool LC, Rackham O, Filipovska A (2017) Adult-onset obesity is triggered by impaired mitochondrial gene expression. Sci Adv 3:e1700677.

» PMID: 28835921 Open Access

Perks KL, Ferreira N, Richman TR, Ermer JA, Kuznetsova I, Shearwood AJ, Lee RG, Viola HM, Johnstone VPA, Matthews V, Hool LC, Rackham O, Filipovska A (2017) Sci Adv

Abstract: Mitochondrial gene expression is essential for energy production; however, an understanding of how it can influence physiology and metabolism is lacking. Several proteins from the pentatricopeptide repeat (PPR) family are essential for the regulation of mitochondrial gene expression, but the functions of the remaining members of this family are poorly understood. We created knockout mice to investigate the role of the PPR domain 1 (PTCD1) protein and show that loss of PTCD1 is embryonic lethal, whereas haploinsufficient, heterozygous mice develop age-induced obesity. The molecular defects and metabolic consequences of mitochondrial protein haploinsufficiency in vivo have not been investigated previously. We show that PTCD1 haploinsufficiency results in increased RNA metabolism, in response to decreased protein synthesis and impaired RNA processing that affect the biogenesis of the respiratory chain, causing mild uncoupling and changes in mitochondrial morphology. We demonstrate that with age, these effects lead to adult-onset obesity that results in liver steatosis and cardiac hypertrophy in response to tissue-specific differential regulation of the mammalian target of rapamycin pathways. Our findings indicate that changes in mitochondrial gene expression have long-term consequences on energy metabolism, providing evidence that haploinsufficiency of PTCD1 can be a major predisposing factor for the development of metabolic syndrome.


Bioblast editor: Kandolf G O2k-Network Lab: AU Perth Filipovska A


Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Heart, Liver  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS  HRR: Oxygraph-2k 

Labels, 2017-12