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Title: Coordination of mitochondrial and lysosomal homeostasis mitigates inflammation and muscle atrophy during aging
Author: Irazoki, Andrea
Martinez-Vicente, Marta
Aparicio, Pilar
Aris, Cecilia
Alibakhshi, Esmaeil
Rubio Valera, Maria
Castellanos, Juan
Lores Obradors, Luis
Palacín Prieto, Manuel
Gumà i Garcia, Anna Maria
Zorzano Olarte, Antonio
Sebastián Muñoz, David
Keywords: Inflamació
Issue Date: 9-Mar-2022
Publisher: John Wiley & Sons
Abstract: Sarcopenia is one of the main factors contributing to disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BNIP3 plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of TLR9-dependent inflammation and activation of the NLRP3 inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age-induced muscle inflammation in mouse and humans. Taken together, our data allows us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key in maintaining muscle health during aging.
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It is part of: Aging Cell, 2022, vol. 21, num. 4, p. e13583
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ISSN: 1474-9718
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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