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Biological effects of the loss of homochirality in a multicellular organism
Date
2022
Abstract
Homochirality is a fundamental feature of all known forms of life, maintaining biomolecules (amino-acids, proteins, sugars, nucleic acids) in one specific chiral form. While this condition is central to biology, the mechanisms by which the adverse accumulation of non-L-α-amino-acids in proteins lead to pathophysiological consequences remain poorly understood. To address how heterochirality build-up impacts organism’s health, we use chiral-selective in vivo assays to detect protein-bound non-L-α-amino acids (focusing on aspartate) and assess their functional significance in Drosophila. We find that altering the in vivo chiral balance creates a ‘heterochirality syndrome’ with impaired caspase activity, increased tumour formation, and premature death. Our work shows that preservation of homochirality is a key component of protein function that is essential to maintain homeostasis across the cell, tissue and organ level.
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Description
Publisher
Nature Research
Citation
Nature Communications, 13, 7059
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Funding Information
Université Côte d’Azur (UCA), IDEX- Initiative d’excellence Grant (A.B.), SOLEIL Synchrotron grant, Project number 20181617 (A.B.), SOLEIL Synchrotron grant, Project number 20180582 (A.B.), Science Foundation Ireland (SFI) grant, award number 12/RC/2275_P2 (DT), ERC starting grant CellSex, Grant number: ERC-2019-STG#850934 (B.H.). Work in SN laboratory is supported by Agence Nationale pour la Recherche (ANR-17-CE13-0024; ANR-20-CE13-0004), Fondation pour la Recherche Médicale (FRM; EQU201903007825), Université Côte d’Azur (UCA), Centre National pour la Recherche Scientifique (CNRS), Institut National pour la Recherche Médicale (Inserm), LABEX SIGNALIFE (ANR-11-LABX-0028-01).