NDUFS2 Mitochondrial Complex I Deficiency Induces Adipose Tissue Degeneration Via IIS in a Drosophila Melanogaster Model

PhD Programme in Molecular Biosciences BIO 05

NDUFS2 Mitochondrial Complex I deficiency induces adipose tissue degeneration via IIS in a Drosophila melanogaster model. José María Becedas1, Alba Rocío Tornero1, Roberto Serna1, Sara Laine-Menéndez1, Sonia Rodríguez1, Rafael Garesse1, Margarita Cervera1, Juan José Arredondo1*

1Departamento de Bioquímica (Facultad de Medicina-UAM) & Instituto de Investigaciones Biomédicas Alberto Sols (CSIC), Madrid, Spain. *Corresponding author: Juan José Arredondo, UAM- CSIC, Madrid, Spain. E-mail: [email protected]

Cardiac diseases are the foremost cause of death due to health problems in the western society. Amongst the causes of cardiac disease, those caused by metabolic defects, especially mitochondrial inborn errors, have difficult treatment and prognosis. This organelle provides energy trough oxidative phosphorylation, abbreviated as OXPHOS, and participates in apoptotic pathways. Permanent OXPHOS metabolism decay due to deficiencies in electron transport chain genes activates cell-signalling routes, leading to tissue wasting and disease. To study these diseases, we decide to develop a Drosophila melanogaster model in which nuclear encoded respiratory chain gene NDUFS2 has been specifically interfered in indirect flight skeletal-like muscle using UAS-GAL4 system. NDUFS2 is a structural subunit of the complex I core reported to cause hypertrophic cardiomyopathy among other symptoms. NDUFS2 IFM specific interference causes muscle and fat bodies degeneration, although the last ones are not NDUFS2 interfered and present healthy mitochondria. Gene expression assays indicate that the phenotype of wasted skeletal muscle leads to the increased expression of Impl2 gene in this tissue. Impl2 is an inhibitor of insulin/ insulin-like growth factor signalling. We suggest Impl2 overexpression induces lipid and glucose mobilization, and therefore, the observed fat bodies reduction leading to a phenotype reminiscent to insulin resistance and lipodystrophy in mammals. These results highlight the importance of knowing the routes triggered by mitochondrial malfunction and, thereafter, the tissue metabolic interdependence involved.

Keywords: mitochondria, Drosophila, NDUFS2, cardiomyopathy. Published May 18, 2018. Copyright: © 2017 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Editor:- Cite as: José María Becedas, Alba Rocío Tornero, Roberto Serna, Sara Laine-Menéndez, Sonia Rodríguez, Rafael Garesse, Margarita Cervera, Juan José Arredondo. NDUFS2 Mitochondrial Complex I deficiency induces adipose tissue degeneration via IIS in a Drosophila melanogaster model. IBJ Plus 2018 (S2):e00005 doi: 10.24217/2531-0151.18v1s2.00005. Funding: Fondo de Investigaciones Sanitarias (IP: Rafael Garasse). Competing Interests:No conflict of interests exists.