Figure 1.

GRAMD1C is an ER cholesterol transfer protein that interacts with mitochondria via its GRAM domain to facilitate mitochondria-ER cholesterol transfer. Cells lacking GRAMD1C expression show increased autophagic flux and a concomitant increase in mitochondrial cholesterol levels and mitochondrial respiration. By maintaining cholesterol levels at ER membranes, GRAMD1C likely contributes to the suppression of autophagosome biogenesis and regulation of mitochondrial bioenergetics, potentially contributing to the decreased survival of ccRCC patients with low GRAMD1C levels. Figure generated with Biorender.