Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury.

The role of insulin receptor (IR) activated by hyperinsulinemia in obesity-induced kidney injury is not well understood. We hypothesized that activation of kidney proximal tubule epithelial IR contributes to obesity-induced kidney injury. We administered normal-fat diet (NFD) or high-fat diet (HFD) to control and kidney proximal tubule IR-knockout (KPTIRKO) mice for 4 months.

Lactate Elicits ER-Mitochondrial Mg Dynamics to Integrate Cellular Metabolism.

Mg is the most abundant divalent cation in metazoans and an essential cofactor for ATP, nucleic acids, and countless metabolic enzymes. To understand how the spatio-temporal dynamics of intracellular Mg (Mg) are integrated into cellular signaling, we implemented a comprehensive screen to discover regulators of Mg dynamics. Lactate emerged as an activator of rapid release of Mg from endoplasmic reticulum (ER) stores, which facilitates mitochondrial Mg (Mg) uptake in multiple cell types.

Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity.

The tricarboxylic acid (TCA) cycle converts the end products of glycolysis and fatty acid β-oxidation into the reducing equivalents NADH and FADH Although mitochondrial matrix uptake of Ca enhances ATP production, it remains unclear whether deprivation of mitochondrial TCA substrates alters mitochondrial Ca flux. We investigated the effect of TCA cycle substrates on MCU-mediated mitochondrial matrix uptake of Ca, mitochondrial bioenergetics, and autophagic flux. Inhibition of glycolysis, mitochondrial pyruvate transport, or mitochondrial fatty acid transport triggered expression of the MCU gatekeeper MICU1 but not the MCU core subunit.