Biological effects of the loss of homochirality in a multicellular organism

Active regulation of chirality, or handedness, is crucial for life. Here, the authors describe assays to characterise proteome chirality in vivo and show that errors degrade enzyme activity triggering tumour formation and reduced lifespan. 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-alpha-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-alpha-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.

Automated summary

Active regulation of chirality is crucial for life, as the preservation of homochirality is essential for maintaining protein function and overall organism health. Accumulation of heterochirality leads to impaired enzyme activity, increased tumor formation, and reduced lifespan.