Biological effects of the loss of homochirality in a multicellular organism
Ágnes Bánréti, Shayon Bhattacharya, Frank Wien, Koichi Matsuo, Matthieu Réfrégiers, Cornelia Meinert, Uwe J. Meierhenrich, Bruno Hudry, Damien Thompson, Stéphane Noselli
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.