mPOS is a novel mitochondrial trigger of cell death - implications for neurodegeneration

FEBS Letters
Liam P Coyne, Xin Jie Chen

Abstract

In addition to its central role in energy metabolism, the mitochondrion has many other functions essential for cell survival. When stressed, the multifunctional mitochondria are expected to engender multifaceted cell stress with complex physiological consequences. Potential extra-mitochondrial proteostatic burdens imposed by inefficient protein import have been largely overlooked. Accumulating evidence suggests that a diverse range of pathogenic mitochondrial stressors, which do not directly target the core protein import machinery, can reduce cell fitness by disrupting the proteostatic network in the cytosol. The resulting stress, named mitochondrial precursor overaccumulation stress (mPOS), is characterized by the toxic accumulation of unimported mitochondrial proteins in the cytosol. Here, we review our current understanding of how mitochondrial dysfunction can impact the cytosolic proteome and proteostatic signaling. We also discuss the intriguing possibility that the mPOS model may help untangle the cause-effect relationship between mitochondrial dysfunction and cytosolic protein aggregation, which are probably the two most prominent molecular hallmarks of neurodegenerative disease.

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Citations

Aug 31, 2018·FEMS Yeast Research·Nicoletta GuaragnellaSergio Giannattasio
Aug 28, 2020·The Biochemical Journal·Karthik MohanrajAgnieszka Chacinska
Mar 7, 2020·NPJ Genomic Medicine·Jesse Slone, Taosheng Huang
Feb 14, 2021·NPJ Genomic Medicine·Jesse Slone, Taosheng Huang
Apr 20, 2021·Biology of the Cell·Sebabrata Maity, Oishee Chakrabarti
Aug 22, 2021·Antioxidants & Redox Signaling·Eftekhar Eftekharpour, Paul Fernyhough
Aug 26, 2021·Molecular Biology Reports·Jing ZhengXiang Yu
Sep 12, 2021·Oncogene·Shanna DewaelePieter Mestdagh
Jan 4, 2022·ACS Biomaterials Science & Engineering·Naoto Yoshinaga, Keiji Numata

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