Lindfors 2011 Proc Natl Acad Sci U S A

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Lindfors C, Nilsson IA, Garcia-Roves PM, Zuberi AR, Karimi M, Donahue LR, Roopenian DC, Mulder J, Uhlen M, Ekstroem TJ, Davisson MT, Hoekfelt TG, Schalling M, Johansen JE (2011) Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse. Proc Natl Acad Sci U S A 108:18108-13.

» PMCID: PMC3207677 Open Access

Lindfors C, Nilsson IA, Garcia-Roves PM, Zuberi AR, Karimi M, Donahue LR, Roopenian DC, Mulder J, Uhlen M, Ekstroem TJ, Davisson MT, Hoekfelt TG, Schalling M, Johansen JE (2011) Proc Natl Acad Sci U S A

Abstract: The anorectic anx/anx mouse exhibits disturbed feeding behavior and aberrances, including neurodegeneration, in peptidergic neurons in the appetite regulating hypothalamic arcuate nucleus. Poor feeding in infants, as well as neurodegeneration, are common phenotypes in human disorders caused by dysfunction of the mitochondrial oxidative phosphorylation system (OXPHOS). We therefore hypothesized that the anorexia and degenerative phenotypes in the anx/anx mouse could be related to defects in the OXPHOS. In this study, we found reduced efficiency of hypothalamic OXPHOS Complex I assembly and activity in the anx/anx mouse. We also recorded signs of increased oxidative stress in anx/anx hypothalamus, possibly as an effect of the decreased hypothalamic levels of fully assembled Complex I, that were demonstrated by native Western blots. Furthermore, the Ndufaf1 gene, encoding a Complex I assembly factor, was genetically mapped to the anx interval and found to be down-regulated in anx/anx mice. These results suggest that the anorexia and hypothalamic neurodegeneration of the anx/anx mouse are associated with dysfunction of mitochondrial Complex I.

Keywords: Anorexia, hypothalamus

O2k-Network Lab: ES_Barcelona_Garcia-Roves PM, SE_Stockholm_Morein T


Labels: MiParea: Respiration 

Stress:Oxidative stress;RONS, Mitochondrial disease  Organism: Mouse  Tissue;cell: Nervous system 

Enzyme: Complex I, Complex II;succinate dehydrogenase 

Coupling state: OXPHOS 

HRR: Oxygraph-2k