The atypical cadherin fat directly regulates mitochondrial function and metabolic state.

Anson Sing, Yonit Tsatskis, Lacramioara Fabian, Ian Hester, Robyn Rosenfeld, Mauro Serricchio, Norman Yau, Maïlis Bietenhader, Riya Shanbhag, Andrea Jurisicova, Julie A. Brill, G. Angus McQuibban, Helen McNeill

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Fat (Ft) cadherins are enormous cell adhesion molecules that function at the cell surface to regulate the tumor-suppressive Hippo signaling pathway and planar cell polarity (PCP) tissue organization. Mutations in Ft cadherins are found in a variety of tumors, and it is presumed that this is due to defects in either Hippo signaling or PCP. Here, we show Drosophila Ft functions in mitochondria to directly regulate mitochondrial electron transport chain integrity and promote oxidative phosphorylation. Proteolytic cleavage releases a soluble 68 kDa fragment (Ft(mito)) that is imported into mitochondria. Ft(mito) binds directly to NADH dehydrogenase ubiquinone flavoprotein 2 (Ndufv2), a core component of complex I, stabilizing the holoenzyme. Loss of Ft leads to loss of complex I activity, increases in reactive oxygen species, and a switch to aerobic glycolysis. Defects in mitochondrial activity in ft mutants are independent of Hippo and PCP signaling and are reminiscent of the Warburg effect.

Original languageEnglish
Pages (from-to)1293-1308
Number of pages16
Issue number6
StatePublished - 2014


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