bims-smemid 2024-03-24 papers

Mol Cell. 2024 Mar 21. pii: S1097-2765(24)00168-0. [Epub ahead of print]84(6): 995-997

Integrating the response to stressed mitochondria.

Chakrabarty et al.1 demonstrate that phospho-EIF2α (pEIF2α), the translation initiation factor that mediates the integrated stress response (ISR), is necessary and sufficient for the autophagic degradation of mitochondria following the addition of mitochondrial stressors.

DOI: https://doi.org/10.1016/j.molcel.2024.02.026

Cell Rep. 2024 Mar 19. pii: S2211-1247(24)00304-8. [Epub ahead of print]43(4): 113976

Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control.

Anna M Smirnova, Vladislava Hronová, Mahabub Pasha Mohammad, Anna Herrmannová, Stanislava Gunišová, Denisa Petráčková, Petr Halada, Štěpán Coufal, Michał Świrski, Justin Rendleman, Kristína Jendruchová, Maria Hatzoglou, Petra Beznosková, Christine Vogel, Leoš Shivaya Valášek.

Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4's induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4's translational control is more complex than originally described, underpinning its key role in diverse biological processes.

Keywords: ATF4; CP: Molecular biology; integrated stress response; ribosome; ribosome queuing; translation reinitiation; translational control; unfolded protein response

DOI: https://doi.org/10.1016/j.celrep.2024.113976

bioRxiv. 2024 Mar 07. pii: 2024.03.05.583623. [Epub ahead of print]

A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity.

Mitochondrial oxidative phosphorylation (OxPhos) powers brain activity 1,2 , and mitochondrial defects are linked to neurodegenerative and neuropsychiatric disorders 3,4 , underscoring the need to define the brain's molecular energetic landscape 5-10 . To bridge the cognitive neuroscience and cell biology scale gap, we developed a physical voxelization approach to partition a frozen human coronal hemisphere section into 703 voxels comparable to neuroimaging resolution (3×3×3 mm). In each cortical and subcortical brain voxel, we profiled mitochondrial phenotypes including OxPhos enzyme activities, mitochondrial DNA and volume density, and mitochondria-specific respiratory capacity. We show that the human brain contains a diversity of mitochondrial phenotypes driven by both topology and cell types. Compared to white matter, grey matter contains >50% more mitochondria. We show that the more abundant grey matter mitochondria also are biochemically optimized for energy transformation, particularly among recently evolved cortical brain regions. Scaling these data to the whole brain, we created a backward linear regression model integrating several neuroimaging modalities 11 , thereby generating a brain-wide map of mitochondrial distribution and specialization that predicts mitochondrial characteristics in an independent brain region of the same donor brain. This new approach and the resulting MitoBrainMap of mitochondrial phenotypes provide a foundation for exploring the molecular energetic landscape that enables normal brain functions, relating it to neuroimaging data, and defining the subcellular basis for regionalized brain processes relevant to neuropsychiatric and neurodegenerative disorders.

DOI: https://doi.org/10.1101/2024.03.05.583623

Photochem Photobiol. 2024 Mar 19.

Compound collagen peptide powder improves skin photoaging by reducing oxidative stress and activating TGF-β1/Smad pathway.

Kaien Guo, Linxin Zheng, Xin Zeng, Guangchun Huang, Lingling Meng, Yuting Yin.

Fish collagen peptide (FCP) has been extensively investigated as a natural product that can combat photoaging; however, its efficacy is limited by its singular composition. Compound collagen peptide powder (CCPP) is a novel functional food formulation that exhibits photoprotective properties and comprises FCP and a blend of natural botanical ingredients. The objective of this study was to investigate the efficacy of CCPP and its molecular mechanism. CCPP had a low molecular weight, facilitating its efficient absorption, and was abundant in amino acids, total polyphenols, and total flavonoids. The results of in vivo studies demonstrated that CCPP exhibited significant efficacy in reducing skin wrinkles, enhancing the contents of water and oil in the skin, and ameliorating histopathological alterations in mice. The results of in vitro studies demonstrated that CCPP effectively mitigated photoaging in human skin fibroblasts by attenuating oxidative stress and promoting extracellular matrix (ECM) synthesis. Moreover, we clearly demonstrated that the TGF β1/Smad pathway was involved in the promotion of ECM synthesis and cell proliferation by CCPP in human skin fibroblasts. These findings suggest that, compared with single collagen, CCPP has a more comprehensive range of antiphotoaging properties.

Keywords: TGF-β1/Smad pathway; compound collagen peptide powder; fish collagen peptide; oxidative stress; photoaging

DOI: https://doi.org/10.1111/php.13940