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Updated: Feb 19, 2026
Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
mPOS is a novel mitochondrial trigger of cell death - implications for neurodegeneration
Liam P Coyne1, Xin Jie Chen1,2
1Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY, USA.
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.
Insights
Mitochondrial dysfunction can cause toxic protein buildup in the cell
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Neuroscience
Background:
- Mitochondria are vital for cell survival beyond energy metabolism.
- Mitochondrial dysfunction can lead to complex cellular stress responses.
- The impact of mitochondrial dysfunction on cytosolic proteostasis is underappreciated.
Purpose of the Study:
- To review the impact of mitochondrial dysfunction on the cytosolic proteome and proteostatic signaling.
- To explore the role of mitochondrial precursor overaccumulation stress (mPOS) in cellular health.
- To discuss the potential link between mPOS and neurodegenerative diseases.
Main Methods:
- Literature review of mitochondrial dysfunction and proteostasis.
- Analysis of evidence linking mitochondrial stressors to cytosolic protein aggregation.
- Discussion of the mPOS model and its implications.
Main Results:
- Mitochondrial stressors, not directly affecting protein import, can disrupt cytosolic proteostasis.
- Mitochondrial precursor overaccumulation stress (mPOS) results from toxic accumulation of unimported mitochondrial proteins.
- Dysfunctional mitochondria can negatively impact cellular fitness by overwhelming the cytosolic proteome.
Conclusions:
- Mitochondrial dysfunction has significant, often overlooked, consequences for cytosolic proteostasis.
- The mPOS model provides a framework for understanding how mitochondrial issues affect cellular protein balance.
- mPOS may be a key factor in the pathogenesis of neurodegenerative diseases characterized by protein aggregation.
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