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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
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Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function
Karen Rosier1, Molly T McDevitt2, Joél Smet3
1Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven, Belgium.
Iscience
|December 10, 2021
Summary
Prolyl endopeptidase-like (PREPL) deficiency impacts mitochondrial function and gene expression, leading to metabolic disorders. This study reveals PREPL acts as a depalmitoylase, crucial for mitochondrial homeostasis.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Prolyl endopeptidase-like (PREPL) deficiency causes a rare metabolic disorder.
- The precise role and substrates of PREPL are not well understood.
Purpose of the Study:
- To investigate the function of PREPL in cellular processes.
- To elucidate the role of PREPL in mitochondrial homeostasis and gene expression.
Main Methods:
- Protein-protein interaction analysis
- Mitochondrial complex activity assays
- Gene expression analysis
- Mitochondrial ultrastructure examination
- Enzyme activity assays
- Crystal structure determination
Main Results:
- The long PREPL isoform (PREPLL) localizes to mitochondria.
- PREPL deficiency in mice impairs mitochondrial complex activities and gene expression.
- Mitochondrial ultrastructure is abnormal in PREPL-deficient patients and mice.
- PREPL exhibits (thio)esterase activity, suggesting a depalmitoylating function.
Conclusions:
- PREPL functions as a (thio)esterase, not a peptidase.
- PREPLL plays a critical role in maintaining mitochondrial homeostasis.
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