Proceedings of The Physiological Society

Mitochondria: Form and function (London, UK) (2017) Proc Physiol Soc 38, SA06

Research Symposium

Role of mitochondrial fusion proteins on liver metabolism.

A. Zorzano1,2,3

1. Institute for Research in Biomedicine, BARCELONA, Spain. 2. Biochemistry & Molecular Biology, University of Barcelona, Barcelona, Barcelona, Spain. 3. CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, BARCELONA, Barcelona, Spain.

Mitochondrial fusion and fission are key processes regulating mitochondrial morphology. Mitochondrial fusion is catalyzed by Mfn1, Mfn2 and OPA1 in mammalian cells. Mfn1 and Mfn2 are transmembrane GTPases localized in the outer mitochondrial membrane and involved in tethering and fusion. Mfn2 protein seems to play a complex set of functional roles, and it also controls endoplasmic reticulum morphology and function. Liver-specific ablation of Mfn2 in mice causes numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency also impaired insulin signaling in liver. Furthermore, Mfn2 deficiency was associated with endoplasmic reticulum stress, enhanced hydrogen peroxide concentration, altered reactive oxygen species handling, and active JNK. In contrast, livers upon ablation of Mfn1 showed an enhanced mitochondrial respiration capacity and protection against insulin resistance induced by a high-fat diet. This pattern of changes suggests that Mfn1 and Mfn2 play distinct roles in hepatocytes or they induce an opposite pattern of adaptations upon loss-of-function.

Where applicable, experiments conform with Society ethical requirements