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Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of antigen-processing and presentation components.

Latorre-Muro et al. show that the cytosolic chaperone PPID drives insertion of the mitochondrial import receptor TOM70 into the mitochondrial outer membrane, thereby regulating body temperature, glucose homeostasis and body weight in obese mice.

Melanoma phenotypic switching contributes to targeted BRAF treatment resistance. Here the authors identify a subset of BRAF treatment-resistant melanomas with suppressed PGC1a expression that are sensitive to HMGCR inhibitors.

Yin et al. identify miR-155–IFN-γ signaling that regulates a protective microglial subset in a mouse model of Alzheimer’s disease. These microglia enhance plaque compaction, reduce dystrophic neurites and synaptic degradation, and improve cognition.

Discovery of a biochemical mechanism through which lactate binds and inhibits the SUMO protease SENP1, stimulating timed degradation of cell cycle proteins, and resulting in mitotic exit.

A chemical screen identifies DHODH inhibitors as robust activators of mitochondrial respirasome assembly. Lipidomics reveal that peroxisomal-derived ether phospholipids accumulate in mitochondria during nucleotide deprivation to drive proliferation.

Mitochondrial oxidative phosphorylation produces ATP and is an important source for cellular energy equivalents. Here the authors perform a cell-based screen to identify genes that alleviate perturbed mitochondrial complex I function and identify malic enzyme (ME-1), which promotes survival by production of NADPH and glutathione.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

UCP1 is exclusively expressed in brown and beige adipocytes, where it drives thermogenesis through futile substrate cycling. Mills et al. identify a endocrine pathway mediated by the UCP1 catabolic circuit that antagonizes liver inflammation by lowering the concentration of succinate in the liver extracellular fluid.

Vγ6⁺ Vδ1⁺ γδ T cells control tolerance to cold by activating adipocyte IL-17RC and promoting sympathetic innervation of thermogenic adipose tissue in mice.

Upon induction by thermogenic stimuli, creatine kinase B traffics to mitochondria to trigger the futile creatine cycle in thermogenic fat.

Tissue nonspecific alkaline phosphatase (TNAP) within mitochondria hydrolyses phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation in thermogenic fat cells.

miRNAs are incorporated into ribonucleoprotein complexes called RNA-induced silencing complexes (RISCs) to exert RNA interference. Here the authors show that translation initiation factor eIF1A interacts with the RISCs component Ago2 to promote miR-451 biogenesis and RNA interference.

Creatine can be used for thermogenesis in adipocytes. Here Kazak et al. show that creatine uptake is required to sustain this thermogenic pathway. Knockdown of the creatine transporter, CrT, in adipocytes decreases thermogenesis and energy expenditure, whereas creatine supplementation increases energy expenditure in mice fed a high-fat diet.

In mice, expression of PGC1-α in muscles is shown to stimulate expression of FNDC5, which is cleaved and secreted in the circulation as the newly identified hormone irisin; on exercise, this hormone stimulates browning of subcutaneous adipose tissue.

Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.

The newly identified calsyntenin 3β protein has a role in the innervation of thermogenic fat through a mechanism of communication—which is unique to mammals—between thermogenic adipocytes and sympathetic neurons.

WebTreatment of lipopolysaccharide-activated macrophages with the cell-permeable itaconate derivative 4-octyl itaconate activates the anti-inflammatory transcription factor Nrf2 by alkylating key cysteine residues on the KEAP1 protein.

In an unbiased screen, Perry et al. find that tetracycline antibiotics improve resilience of cultured cells carrying disease-associated mitochondrial DNA mutations. Doxycycline is shown to increases survival, and reduce symptoms, in a mouse model of Leigh syndrome.

A comparative metabolomics approach is used to identify succinate as a key activator of thermogenesis in brown adipose tissue.

The Forkhead transcription factors FOXK1 and FOXK2, which are induced by starvation, reprogram cellular metabolism to induce aerobic glycolysis.

Uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue is supported by a burst of mitochondrial reactive oxygen species upon cold exposure.

Microglia are resident myeloid cells of the central nervous system integral for neuroprotective and neurodegenerative processes. Here the authors describe a unique TGF-β dependent molecular and functional microglia signature that distinguishes these cells from other immune and glial cells in the periphery and brain.