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Phosphorylation of the mitochondrial DNA (mtDNA) maintenance factor TFAM during spermatogenesis prevents its import into mitochondria, resulting in elimination of paternal mtDNA and leading to maternal inheritance.
Ernst and Renne highlight two papers, one that discovered and another that structurally defined the ER–mitochondria encounter structure (ERMES) that facilitates the exchange of lipids between the ER and mitochondria.
Eukaryotic membrane fusion is hindered by energy barriers and often requires soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) to facilitate formation of a fusion pore. Recent studies describe SNARE activity along the fusion pathway and shed light on the regulation of SNARE complex assembly.
Embedded within the complexity of biological systems lies a formidable task: deciphering the intricate architecture of macromolecules. In this Viewpoint, a panel of experts discuss the key challenges and opportunities of macromolecular structure determination, highlighting the crucial synergy between empirical experimentation and artificial intelligence-based techniques in unravelling these complexities.
In this Tools of the Trade article, Christine Lim and Alicia González Díaz (Vendruscolo lab) describe a pipeline for the identification and characterization of proteins whose phase separation is altered in disease.
mTOR inhibition by deprivation of the amino acids Tyr, Trp and Phe promotes the translocation of the 26S proteasome from the nucleus to the cytosol, which is required for stress tolerance and cell survival.
Sarkar et al. identify a feedback loop between the methyltransferase SETDB1 and nuclear pore complexes that ensures silencing of early-oogenesis genes as oocyte specification progresses.
Targeted editing of mitochondrial and chloroplast genomes has therapeutic, agricultural and environmental potential, but it is challenging owing to inability of transfecting (guide) RNA into the organelles. Recent designs of protein-only, programmable base editors open promising avenues for organellar DNA editing in cell lines, animals and plants.
A unique feature of mitochondrial DNA function is the coupling of initiation of transcription with that of replication. Tan et al. discuss the choice between initiation of either process, and how mitochondrial DNA packaging into nucleoids controls its accessibility and function in human cells.
Iron homeostasis in animals is tightly controlled, and numerous cellular pathways regulate iron uptake, storage, metabolism and secretion. Recent findings provide new insights into the sensory systems that fine-tune iron homeostasis and explain how cellular and systemic iron fluxes intersect.
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.
