Megalin shuttles hormones (stanniocalcin-1, angiotensin II, TGF-β) from the cell surface to the mitochondria through retrograde early endosomes to Golgi- and Rab32-mediated pathway (PMID: 29916093). Here we show STC1-FLAG expressed in megalin KO cells does not reach the mitochondria; thus, mitochondrial STC1 is extracellularly-derived. Leucines within the signal peptides of megalin and STC1 mediate their interaction; mutations of these leucines and interference with STC1-megalin binding diminishes mitochondrial respiration and glycolysis.
- Qingtian Li
- Michael Holliday
- David Sheikh-Hamad
