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PPTC7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy
Natalie M Niemi1,2, Lia R Serrano3, Laura K Muehlbauer4
1Morgridge Institute for Research, Madison, WI, 53715, USA. niemi@wustl.edu.
Nature Communications
|October 13, 2023
Summary
Protein phosphatase 7 (PPTC7) is crucial for mitochondrial health. Loss of PPTC7 leads to metabolic defects and increased mitophagy, highlighting its role in maintaining mitochondrial function and content.
Area of Science:
- Mitochondrial biology
- Cellular metabolism
- Protein phosphorylation
Background:
- Mitochondrial dysfunction underlies numerous metabolic diseases.
- Protein phosphatase 7 (PPTC7) is a key mitochondrial phosphatase.
- PPTC7 is essential for maintaining mitochondrial content and function.
Purpose of the Study:
- To investigate the role of PPTC7 in adult mice.
- To elucidate the mechanisms by which PPTC7 regulates mitochondrial homeostasis.
- To determine PPTC7's impact on mitophagy.
Main Methods:
- Inducible knockout mouse model
- Phosphoproteomics analysis
- Mitophagy assays in mouse embryonic fibroblasts (MEFs)
- Molecular interaction studies
Main Results:
- Loss of PPTC7 in adult mice reduces mitochondrial mass and metabolic capacity.
- PPTC7 deficiency increases hepatic triglyceride accumulation.
- PPTC7 knockout elevates mitophagy receptor expression (BNIP3, NIX) and activity.
- PPTC7 directly dephosphorylates BNIP3 and NIX.
Conclusions:
- PPTC7 is critical for preventing metabolic defects and premature death.
- PPTC7 regulates mitochondrial function and content through dephosphorylation of key proteins.
- PPTC7 plays a significant role in controlling the mitophagic response.
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