👤 Irma-Sofie Dieter

RNA and proteins are two crucial players in the origin of life but while RNA evolved to assemble proteins from amino acids, a significant mirror-symmetric effect of amino acids to trigger the synthesis of RNA was missing. Here, the authors report ambient alkaline conditions where amino acids, without additional chemical activators, promote RNA copolymerisation more than 100-fold, starting from prebiotically plausible ribonucleoside-2′,3′-cyclic phosphates. Show less

Tumor metastases account for nearly 90% of cancer-related fatalities. To tackle this issue, chemotherapeutic agents that induce immunogenic cell death (ICD) are being investigated as promising candidates for metastatic cancer treatment. Herein, the chemical synthesis and biological evaluation of a novel Ga(III) complex with Schiff bases, [Ga((E)-1-((quinolin-8-ylimino)methyl)naphthalen-2-olato)₂][Cl], for potential use in combined chemotherapy and immunotherapy are reported. This compound exhibited broad cytotoxicity against human breast cancer, pancreatic cancer, cervical cancer cell lines, and the noncancerous human fibroblast cell line. Mechanistic investigations revealed that the compound triggers apoptosis and ICD hallmarks, such as translocation of calreticulin, phosphorylation of eIF2α, migration of high mobility group protein 1, and release of adenosine triphosphate. Deeper biological assessment using multicellular tumor spheroids of cervical cancer cell lines, a solid tumor model, demonstrated successful eradication at micromolar concentrations. This study presents one of the few reported Ga(III) complexes capable of inducing immunogenic cell death. Show less

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease. Show less

High-resolution (≤1.2 Å) structures of functional states of bacteriorhodopsin reveal the molecular mechanism for generating a membrane proton electrochemical gradient, a key event of cell bioenergetics driving ATP synthesis. Show less

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field. Show less