Local coordination of mRNA storage and degradation near mitochondria modulates C. elegans ageing

• Main Author: Daskalaki, Ioanna
• Publication Date: 2023
• Other Authors: Markaki, Maria, Gkikas, Ilias, Tavernarakis, Nektarios
• Format: Article
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: https://hdl.handle.net/10316/116165; https://doi.org/10.15252/embj.2022112446
• topic: Ageing; mRNA metabolism; Mitochondria; Protein synthesis; Stress; Animals; Aging; Mitochondria; Longevity; Caenorhabditis elegans; Caenorhabditis elegans Proteins

Mitochondria are central regulators of healthspan and lifespan, yet the intricate choreography of multiple, tightly controlled steps regulating mitochondrial biogenesis remains poorly understood. Here, we uncover a pivotal role for specific elements of the 5'-3' mRNA degradation pathway in the regulation of mitochondrial abundance and function. We find that the mRNA degradation and the poly-A tail deadenylase CCR4-NOT complexes form distinct foci in somatic Caenorhabditis elegans cells that physically and functionally associate with mitochondria. Components of these two multi-subunit complexes bind transcripts of nuclear-encoded mitochondria-targeted proteins to regulate mitochondrial biogenesis during ageing in an opposite manner. In addition, we show that balanced degradation and storage of mitochondria-targeted protein mRNAs are critical for mitochondrial homeostasis, stress resistance and longevity. Our findings reveal a multifaceted role of mRNA metabolism in mitochondrial biogenesis and show that fine-tuning of mRNA turnover and local translation control mitochondrial abundance and promote longevity in response to stress and during ageing.