Trends in Biochemical Sciences最新文献

Pluripotent stem cells hold great promise as an unlimited resource for regenerative medicine due to their capacity to self-renew and differentiate into various cell types. Chemical reprogramming using small molecules precisely regulates cell signaling pathways and epigenetic states, providing a novel approach for generating human pluripotent stem cells. Since its successful establishment in 2022, human chemical reprogramming has rapidly achieved significant progress, demonstrating its significant potential in regenerative medicine. Mechanistic analyses have revealed distinct molecular pathways and regulatory mechanisms unique to chemical reprogramming, differing from traditional transcription-factor-driven methods. In this review we highlight recent advancements in our understanding of the mechanisms of human chemical reprogramming, with the goal of enhancing insights into the principles of cell fate control and advancing regenerative medicine.

It has long been established that heat represents a major part of the energy released during the oxidation of mitochondrial substrates. However, with a few exceptions, the release of heat is rarely mentioned other than as being produced at the expense of ATP, without having any specific function. Here, after briefly surveying the literature on mitochondrial heat production, we argue for its cellular and organismal importance, sharing our opinions as to what could account for this unbalanced portrayal of mitochondrial energy transactions.

Much of our understanding of RNA-protein interactions, and how these interactions shape gene expression and cell state, have come from studies looking at these interactions in vitro or inside the cell. However, recent data demonstrates the presence of extracellular and cell surface-associated RNA such as glycosylated RNA (glycoRNA), suggesting an entirely new environment and cellular topology in which to study RNA-RNA binding protein (RBP) interactions. Here, we explore emerging ideas regarding the landscape of cell surface RNA and RBPs. We also discuss open questions concerning the trafficking and anchoring of RBPs to the cell surface, whether cell surface RBPs (csRBPs) directly interact with cell surface RNA, and how changes in the presentation of csRBPs may drive autoimmune responses.

Mitochondrial function relies on the precise targeting and import of cytosolic proteins into mitochondrial subcompartments. Most matrix-targeted proteins follow the presequence pathway, which directs precursor proteins across the outer mitochondrial membrane (OMM) via the Translocase of the Outer Membrane (TOM) complex and into the matrix or inner mitochondrial membrane (IMM) via the Translocase of the Inner Membrane 23 (TIM23) complex. While classical biochemical studies provided detailed mechanistic insights into the composition and mechanism of the TIM23 complex, recent cryogenic-electron microscopy (cryo-EM) data challenge these established models and propose a revised model of translocation in which the TIM17 subunit acts as a 'slide' for precursor proteins, with Tim23 acting as a structural element. In this review, we summarize existing models, highlighting the questions and data needed to reconcile these perspectives, and enhance our understanding of TIM23 complex function.

Autophagy is an intracellular degradation system that delivers cytoplasmic materials to the lysosome. S-acylation, a reversible post-translational modification that attaches long-chain fatty acids to cysteine residues within proteins, has recently emerged as an important regulatory mechanism for autophagy. In this forum article, we review and discuss the emerging roles of S-acylation in autophagy.

Deaminases belonging to the AID/APOBEC family are known as ssDNA and mRNA mutators involved in innate/adaptive immunity, mRNA editing, genome stabilization by restricting retrotransposons, and carcinogenesis. Recent studies suggest that the repertoire of AID/APOBEC targets is more diverse than previously thought and imply a broader biological impact of these proteins.