Journal
EMBO JOURNAL
Volume 42, Issue 16, Pages -Publisher
WILEY
DOI: 10.15252/embj.2022112446
Keywords
ageing; mitochondria; mRNA metabolism; protein synthesis; stress
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Mitochondria play a crucial role in healthspan and lifespan regulation, but the regulatory steps involved in mitochondrial biogenesis are still poorly understood. This study reveals that specific elements of the mRNA degradation pathway are essential for regulating mitochondrial abundance and function. The mRNA degradation and poly-A tail deadenylase CCR4-NOT complexes were found to physically and functionally associate with mitochondria in somatic cells of Caenorhabditis elegans. These complexes bind to transcripts of nuclear-encoded mitochondria-targeted proteins and regulate mitochondrial biogenesis in opposite ways during aging. Additionally, balanced degradation and storage of mitochondria-targeted protein mRNAs are important for maintaining mitochondrial homeostasis, stress resistance, and longevity. These findings highlight the multifaceted role of mRNA metabolism in mitochondrial biogenesis and demonstrate the importance of fine-tuning mRNA turnover and local translation for mitochondrial abundance and longevity in response to stress and aging.
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 & PRIME;-3 & PRIME; 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.
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