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Complex III Releases Superoxide to Both Sides of the Inner Mitochondrial Membrane*
It is demonstrated that Complex I-dependent superoxide is exclusively released into the matrix and that no detectable levels escape from intact mitochondria, fitting well with the proposed site of electron leak at Complex I.
Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production.
Enhanced generation of mitochondrial ROS may be a common factor in the mechanism underlying denervation-induced atrophy in aging, mice lacking CuZn-SOD, and in the neurodegenerative disease, amyotrophic lateral sclerosis.
An inhibitor of oxidative phosphorylation exploits cancer vulnerability
Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis.
Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.
This study used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells and found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma.
Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma
A gradient model of oncogenic NRAS signaling in which the output is gated, resulting in the decoupling of discrete downstream biological phenotypes as a result of incomplete inhibition is suggested, offering a new framework to identify nonobvious coextinction target(s) for combined pharmacological inhibition in NRAS-mutant melanomas.