bims-tricox 2024-02-04 papers

Issue of 2024‒02‒04
three papers selected by
Yash Verma, University of Zurich

Nat Commun. 2024 Feb 02. 15(1): 988

Rescue of mitochondrial import failure by intercellular organellar transfer.

Hope I Needs, Emily Glover, Gonçalo C Pereira, Alina Witt, Wolfgang Hübner, Mark P Dodding, Jeremy M Henley, Ian Collinson.

Mitochondria are the powerhouses of eukaryotic cells, composed mostly of nuclear-encoded proteins imported from the cytosol. Thus, problems with the import machinery will disrupt their regenerative capacity and the cell's energy supplies - particularly troublesome for energy-demanding cells of nervous tissue and muscle. Unsurprisingly then, import breakdown is implicated in disease. Here, we explore the consequences of import failure in mammalian cells; wherein, blocking the import machinery impacts mitochondrial ultra-structure and dynamics, but, surprisingly, does not affect import. Our data are consistent with a response involving intercellular mitochondrial transport via tunnelling nanotubes to import healthy mitochondria and jettison those with blocked import sites. These observations support the existence of a widespread mechanism for the rescue of mitochondrial dysfunction.

DOI: https://doi.org/10.1038/s41467-024-45283-2

Methods Cell Biol. 2024 ;pii: S0091-679X(22)00147-9. [Epub ahead of print]181 87-108

Assessing chronological aging in Saccharomyces cerevisiae.

Adina Schulze, Andreas Zimmermann, Katharina Kainz, Nadine B Egger, Maria A Bauer, Frank Madeo, Didac Carmona-Gutierrez.

Chronological age represents the time that passes between birth and a given date. To understand the complex network of factors contributing to chronological lifespan, a variety of model organisms have been implemented. One of the best studied organisms is the yeast Saccharomyces cerevisiae, which has greatly contributed toward identifying conserved biological mechanisms that act on longevity. Here, we discuss high- und low-throughput protocols to monitor and characterize chronological lifespan and chronological aging-associated cell death in S. cerevisiae. Included are propidium iodide staining with the possibility to quantitatively assess aging-associated cell death via flow cytometry or qualitative assessments via microscopy, cell viability assessment through plating and cell counting and cell death characterization via propidium iodide/AnnexinV staining and subsequent flow cytometric analysis or microscopy. Importantly, all of these methods combined give a clear picture of the chronological lifespan under different conditions or genetic backgrounds and represent a starting point for pharmacological or genetic interventions.

Keywords: Aging; Apoptosis; Cell death; Chronological lifespan; High-throughput; Necrosis; Viability; Vitality; Yeast

DOI: https://doi.org/10.1016/bs.mcb.2022.09.006

bioRxiv. 2024 Jan 17. pii: 2024.01.16.575914. [Epub ahead of print]

Structural basis of respiratory complexes adaptation to cold temperatures.

Young-Cheul Shin, Pedro Latorre-Muro, Amina Djurabekova, Oleksii Zdorevskyi, Christopher F Bennett, Nils Burger, Kangkang Song, Chen Xu, Vivek Sharma, Maofu Liao, Pere Puigserver.

In response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain (1, 2). Yet, the structural basis of respiratory complex adaptation to cold remains elusive. Herein we combined thermoregulatory physiology and cryo-EM to study endogenous respiratory supercomplexes exposed to different temperatures. A cold-induced conformation of CI:III 2 (termed type 2) was identified with a ∼25° rotation of CIII 2 around its inter-dimer axis, shortening inter-complex Q exchange space, and exhibiting different catalytic states which favor electron transfer. Large-scale supercomplex simulations in lipid membrane reveal how unique lipid-protein arrangements stabilize type 2 complexes to enhance catalytic activity. Together, our cryo-EM studies, multiscale simulations and biochemical analyses unveil the mechanisms and dynamics of respiratory adaptation at the structural and energetic level.

DOI: https://doi.org/10.1101/2024.01.16.575914