Biological effects of the loss of homochirality in a multicellular organism

Agnes Banreti (), Shayon Bhattacharya, Frank Wien, Koichi Matsuo, Matthieu Réfrégiers, Cornelia Meinert, Uwe Meierhenrich, Bruno Hudry, Damien Thompson and Stéphane Noselli
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Agnes Banreti: Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose
Shayon Bhattacharya: University of Limerick
Frank Wien: DISCO Beamline, Synchrotron SOLEIL
Koichi Matsuo: Hiroshima University
Matthieu Réfrégiers: Centre de Biophysique Moléculaire
Cornelia Meinert: Université Côte d’Azur, Institut de Chimie de Nice
Uwe Meierhenrich: Université Côte d’Azur, Institut de Chimie de Nice
Bruno Hudry: Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose
Damien Thompson: University of Limerick
Stéphane Noselli: Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34516-x

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