A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass.

Mitophagy mediated by BNIP3 and NIX critically regulates mitochondrial mass. Cellular BNIP3 and NIX levels are tightly controlled by SCF-mediated ubiquitination to prevent excessive mitochondrial loss and lethal disease. Here, we report that knockout of PPTC7, a mitochondrial matrix protein, hyperactivates BNIP3-/NIX-mediated mitophagy and causes perinatal lethality that is rescued by NIX knockout in mice.

Chronic Stress That Changed Intestinal Permeability and Induced Inflammation Was Restored by Estrogen.

Chronic psychological stress affects the health of humans and animals (especially females or pregnant bodies). In this study, a stress-induced model was established by placing eight-week-old female and pregnant mice in centrifuge tubes for 4 h to determine whether chronic stress affects the intestinal mucosal barrier and microbiota composition of pregnant mice. Compared with the control group, we found that norepinephrine (NE), corticosterone (CORT), and estradiol (E) in plasma increased significantly in the stress group.

A mitochondrial SCF-FBXL4 ubiquitin E3 ligase complex degrades BNIP3 and NIX to restrain mitophagy and prevent mitochondrial disease.

Mitophagy is a fundamental quality control mechanism of mitochondria. Its regulatory mechanisms and pathological implications remain poorly understood. Here, via a mitochondria-targeted genetic screen, we found that knockout (KO) of FBXL4, a mitochondrial disease gene, hyperactivates mitophagy at basal conditions.

Mitochondrial cristae architecture protects against mtDNA release and inflammation.

Mitochondrial damage causes mitochondrial DNA (mtDNA) release to activate the type I interferon (IFN-I) response via the cGAS-STING pathway. mtDNA-induced inflammation promotes autoimmune- and aging-related degenerative disorders. However, the global picture of inflammation-inducing mitochondrial damages remains obscure.