The actin binding protein profilin 1 localizes inside mitochondria and is critical for their function.

Autor:	Read TA; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA. tread@augusta.edu., Cisterna BA; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Skruber K; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA., Ahmadieh S; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, USA.; Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Liu TM; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Vitriol JA; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Shi Y; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.; Department of Population Health Sciences, Medical College of Georgia at Augusta University, Augusta, GA, USA., Black JB; Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA., Butler MT; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA., Lindamood HL; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Lefebvre AE; Calico Life Sciences, South San Francisco, CA, USA., Cherezova A; Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, USA., Ilatovskaya DV; Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, USA., Bear JE; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA., Weintraub NL; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, USA.; Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Vitriol EA; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA. evitriol@augusta.edu.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Aug; Vol. 25 (8), pp. 3240-3262. Date of Electronic Publication: 2024 Jul 18.
DOI:	10.1038/s44319-024-00209-3
Abstrakt:	The monomer-binding protein profilin 1 (PFN1) plays a crucial role in actin polymerization. However, mutations in PFN1 are also linked to hereditary amyotrophic lateral sclerosis, resulting in a broad range of cellular pathologies which cannot be explained by its primary function as a cytosolic actin assembly factor. This implies that there are important, undiscovered roles for PFN1 in cellular physiology. Here we screened knockout cells for novel phenotypes associated with PFN1 loss of function and discovered that mitophagy was significantly upregulated. Indeed, despite successful autophagosome formation, fusion with the lysosome, and activation of additional mitochondrial quality control pathways, PFN1 knockout cells accumulate depolarized, dysmorphic mitochondria with altered metabolic properties. Surprisingly, we also discovered that PFN1 is present inside mitochondria and provide evidence that mitochondrial defects associated with PFN1 loss are not caused by reduced actin polymerization in the cytosol. These findings suggest a previously unrecognized role for PFN1 in maintaining mitochondrial integrity and highlight new pathogenic mechanisms that can result from PFN1 dysregulation. (© 2024. The Author(s).)
Databáze:	MEDLINE
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