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Mitochondrial inorganic polyphosphate is required to maintain proteostasis within the organelle
Journal article   Peer reviewed

Mitochondrial inorganic polyphosphate is required to maintain proteostasis within the organelle

Renata T. Da Costa, Pedro Urquiza, Matheus M. Perez, YunGuang Du, Mei Li Khong, Haiyan Zheng, Mariona Guitart-Mampel, Pia A. Elustondo, Ernest R. Scoma, Vedangi Hambardikar, …
Frontiers in cell and developmental biology, v 12, 1423208
10 Jul 2024
DOI: https://doi.org/10.3389/fcell.2024.1423208
PMID: 39050895
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.3389/fcell.2024.1423208View
Published, Version of Record (VoR) Open

Abstract

Cell and Developmental Biology
The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer well-conserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Developmental Biology
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