Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse

QC 20220204
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.

Nilsson, Ida A. K.Karolinska Institutet (författare)
Garcia-Roves, Pablo M. (författare)
Zuberi, Aamir R. (författare)
Karimi, MohsenKarolinska Institutet (författare)
Donahue, Leah Rae (författare)
Roopenian, Derry C. (författare)
Mulder, JanKarolinska Institutet (författare)
Uhlén, MathiasDepartment of Biotechnology, AlbaNova University Center, 106 91 Stockholm, Sweden(Swepub:kth)u1dulvmw (författare)
Ekstrom, Tomas J.Karolinska Institutet (författare)
Davisson, Muriel T. (författare)
Hokfelt, Tomas G. M. (författare)
Schalling, MartinKarolinska Institutet (författare)
Johansen, Jeanette E.Karolinska Institutet (författare)
Karolinska InstitutetDepartment of Biotechnology, AlbaNova University Center, 106 91 Stockholm, Sweden (creator_code:org_t)

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences108:44, s. 18108-181130027-84241091-6490

Av författaren/redakt...: Lindfors, Charlo ...; Nilsson, Ida A. ...; Garcia-Roves, Pa ...; Zuberi, Aamir R.; Karimi, Mohsen; Donahue, Leah Ra ...; visa fler...; Roopenian, Derry ...; Mulder, Jan; Uhlén, Mathias; Ekstrom, Tomas J ...; Davisson, Muriel ...; Hokfelt, Tomas G ...; Schalling, Marti ...; Johansen, Jeanet ...; visa färre...

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