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The mitochondrial proteome is highly complex, comprising ~1,000–1,500 proteins in mammals. Recent technological advances are now helping to refine the mitochondrial proteome and are assisting in characterizing mitochondrial protein functions, paving the way for better diagnosis and treatment of mitochondrial diseases.
In this Tools of the Trade article, Sarah Paramore (from the Devenport and Nelson labs) discusses the use of mouse strains carrying genomic alterations in PCP genes and how they can increase our understanding of mammalian planar cell polarity.
Antioxidants modulate the levels of reactive oxygen species to allow their physiological roles whilst minimizing the oxidative damage and pathology. The roles and mechanisms of antioxidants are complex and context-dependent, necessitating better understanding of their actions in vivo and warranting caution with their use as therapeutic agents.
Forkhead box (FOXO) transcription factors are important mediators of cell stress responses, generally considered to preserve homeostasis and counteract ageing. However, FOXO-mediated mechanisms can also support the survival of cancer and other dysfunctional cells, thereby complicating the link between FOXOs and lifespan extension.
Antennapedia proteins were among the first proteins found to be exchanged intercellularly. This discovery by Alain Prochiantz and colleagues has inspired researchers of various backgrounds.
Liang et al. show that mitochondria can be expelled from cells via extracellular vesicles as a route of quality control that is an alternative to lysosomal degradation.
In this Review, the authors outline the thermodynamic and kinetic principles of protein misfolding and amyloid formation. Mechanisms of toxicity are discussed, focusing on the effect of amyloid interactions with cellular components, and the association of aggregation with healthy ageing and pathology.
Bulut-Karslıoğlu remembers the publication of two seminal papers that described bivalent chromatin and how this discovery continues to affect research to this day.
To activate noncanonical LC3B lipidation and NLRP3 inflammasome formation, stimulator of interferon genes (STING) forms a proton channel in Golgi membranes.
Anne West recounts the study that showed postnatal accumulation of non-CpG DNA methylation in neurons coinciding with postnatal synapse maturation, suggesting that it contributes to brain function.
In the amphibian axolotl, the kinase mTOR is hyper-sensitive and activates a protein synthesis response that is crucial for wound healing and tissue regeneration.
YAP and TAZ are transcription coactivators with key roles in development and regeneration as well as in cancer. Many of these roles are executed by YAP/TAZ activation in stem cells. This Review discusses how YAP/TAZ regulate stem cell biology, and considers potential applications of modulating YAP/TAZ in regenerative medicine and cancer therapy.
Mechanistic target of rapamycin mTOR complex 1 (mTORC1) is a central regulator of cellular metabolism. Recent studies of the molecular architecture of mTORC1 shed new light on its physiological functions and on the consequences of their dysregulation in cancer, type 2 diabetes and neurodegeneration.
In this Tools of the Trade article, Joleen Cheah (from the Ting lab) discusses the development of TransitID, which allows researchers to capture protein trafficking pathways in vivo without a priori knowledge of specific proteins of interest.
