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. Here, we have performed a mitochondria-targeted CRISPR knockout screen for regulators of the IFN-I response. Strikingly, our screen reveals dozens of hits enriched with key regulators of cristae architecture, including phospholipid cardiolipin and protein complexes such as OPA1, mitochondrial contact site and cristae organization (MICOS), sorting and assembly machinery (SAM), mitochondrial intermembrane space bridging (MIB), prohibitin (PHB), and the F1Fo-ATP synthase. Disrupting these cristae organizers consistently induces mtDNA release and the STING-dependent IFN-I response. Furthermore, knocking out MTX2, a subunit of the SAM complex whose null mutations cause progeria in humans, induces a robust STING-dependent IFN-I response in mouse liver. Taken together, beyond revealing the central role of cristae architecture to prevent mtDNA release and inflammation, our results mechanistically link mitochondrial cristae disorganization and inflammation, two emerging hallmarks of aging and aging-related degenerative diseases.

[Pollution Characteristics and Health Risk Assessment of Hazardous Air Pollutants in the Surroundings of Three Petrochemical Industries in Northwest China].

The samples in the surroundings of three representative petrochemical industries in Northwest China were collected by summa canister/adsorption using activated carbon/glass fiber filter, and then they were analyzed for 13 hazardous air pollutants by gas chromatography-mass spectrometry/gas chromatograph/high performance liquid chromatography. The pollution characteristics and human health risk of hazardous air pollutants were discussed. The results showed that 8 hazardous air pollutants existed in the surroundings of all petrochemical industries. The detection frequency for 8 hazardous air pollutants exceeded 80%. The ranges of the average concentrations of benzene series(BTEX), 1,3-butadiene, 1,4-dichlorobenzene, benzo[a]pyrene were 48.01-182.75 µg·m-3, 6.28-7.95 µg·m-3, 5.53-12.62 µg·m-3 and 7.03-36.08 ng·m-3. Daily average concentration of benzo[a]pyrene was 1.8-13.4 times higher than the limit of national standard level-Ⅱ, and those of benzene, toluene and xylene were also over their limits of standard to different degrees. The non-carcinogenic risks of benzo[a]pyrene and 1,3-butadiene were beyond acceptable levels around the three petrochemical industries in Northwest China. Meanwhile, the non-carcinogenic health impact of benzene was appreciable on the exposed population of Lanzhou petrochemical industrial area. The carcinogenic risks of benzene, ethylbenzene, styrene, 1,3-butadiene, 1,4-dichlorobenzene and benzo[a]pyrene were beyond acceptable levels. At the same time, the carcinogenic risks of benzene, 1,3-butadiene and 1,4-dichlorobenzene were significantly higher than their acceptable ranges recommended by US EPA.