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The perturbation of cholesterol balance can lead to cardiovascular disease, as well as neurodegeneration and cancer. To learn more on cholesterol metabolism and the maintenance of cholesterol homeostasis, see Song and colleagues.
In cells exposed to stiff extracellular matrix, sequestration of the ubiquitin ligase TRIM21 by actin stress fibres can prevent the ubiquitination and breakdown of the glycolytic enzyme PFK, directly linking mechanical sensing to metabolic regulation.
Dan Mishmar recounts the first studies that used mitochondrial DNA (mtDNA) to trace the origin of humanity to Africa and that connected mtDNA mutations with a human disease.
The mTOR pathway integrates diverse environmental cues to control biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing, and is thus a promising target for pharmacological intervention.
Mitochondrial networks are dynamically remodelled via fusion, fission and ultrastructural changes to mitochondrial membranes. These mitochondrial membrane dynamics are tightly coupled to cell function, with morphological changes to mitochondria accompanying a multitude of processes as diverse as cell pluripotency, division, differentiation, senescence and death. Accordingly, disturbed dynamics of mitochondrial membranes are linked to severe human disorders.
Cholesterol is an important structural component of all animal cell membranes that functions in various processes, including membrane dynamics and cell signalling, and is also a precursor of other molecules. Deregulation of cholesterol metabolism — biosynthesis, dietary absorption and cellular uptake, storage and efflux — is linked to many diseases, including cardiovascular and genetic diseases, and cancer. A better understanding of cholesterol metabolism offers the possibility to control systemic cholesterol levels to improve human health.