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Slow TCA flux and ATP production in primary solid tumours but not metastases
Tissues derive ATP from two pathways—glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electrontransport chain. Most energy in mammals is produced via TCA metabolism1. In tumours, however, the absolute rates of these pathways remain unclear. Here we optimize tracer infusion approaches to measure the rates of glycolysis and the TCA cycle in healthy mouse tissues,Kra...
Nature | 2023-04-12
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Spatial mapping of mitochondrial networks and bioenergetics in lung cancer
Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells1. The mitochondria form highly organized networks, in which their outer and inner membrane structures define their bioenergetic capacity2,3. However, in vivo studies delineating the relationship between the structural organization of mitochondrial networks and their bioenergetic activity have been limite...
Nature | 2023-04-12
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Billingham LK, Stoolman JS, Vasan K, Rodriguez AE, Poor TA, Szibor M, Jacobs HT, Reczek CR, Rashidi A, Zhang P, Miska J, Chandel NS
Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation
The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, and its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of the NLRP3 inflammasome through several mechanisms including generation of mitochondrial reactive oxygen species (ROS). Here, we report that mitochondrial electron transport chain (ETC) complex I,...
Nat Immunol | 2022-05-18
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Shi P, Ren X, Meng J, Kang C, Wu Y, Rong Y, Zhao S, Jiang Z, Liang L, He W, Yin Y, Li X, Liu Y, Huang X, Sun Y, Li B, Wu C
Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS
The folded mitochondria inner membrane-cristae is the structural foundation for oxidative phosphorylation (OXPHOS) and energy production. By mechanically simulating mitochondria morphogenesis, we speculate that efficient sculpting of the cristae is organelle non-autonomous. It has long been inferred that folding requires buckling in living systems. However, the tethering force for crista...
Nat Commun | 2022-05-18
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Pan RY, He L, Zhang J, Liu X, Liao Y, Gao J, Liao Y, Yan Y, Li Q, Zhou X, Cheng J, Xing Q, Guan F, Zhang J, Sun L, Yuan Z.
Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease
The pro-inflammatory activation of microglia is a hallmark of Alzheimer's disease (AD), and this process involves a switch from oxidative phosphorylation (OXPHOS) toward glycolysis. Here, we show how a positive feedback loop in microglia drives AD pathogenesis, and we demonstrate that inhibiting this cycle in microglia can ameliorate Aβ burden and cognitive deficits in an AD m...
Cell Metab | 2022-05-18
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Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ
Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects
Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) …
Science | 2022-02-27