Year: 2017
Type: review
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.
Source: FEBS Letters
Authors: Liam P. Coyne, Xin Jie Chen
Institution: SUNY Upstate Medical University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: Aging-related mitochondrial degeneration and degenerative diseases, Role of Ant1 Over-expression and Mitochondrial Damage in Progressive Muscle Degeneration, Mechanism of age-dependent neuromuscular degeneration caused by protein misfolding on the inner mitochondrial membrane, Mechanism of mitochondria-induced cell degeneration in the central nervous system, Mechanism of Mitochondria-induced Progressive Muscle Wasting, G9000215920
OpenAlex ID: W2765793257