Phenotypic CRISPR screens identify NLRX1 as an essential activator of the human mitochondrial permeability transition - PubMed
6 hours ago
- #Mitochondria
- #NLRX1
- #CRISPR
- Phenotypic CRISPR screens identified NLRX1 as an essential activator of the human mitochondrial permeability transition (mPT).
- Two phenotypic assays for mitochondrial calcium overload were designed and applied to FACS-based CRISPR screening in human cells, evaluating 19,113 genes.
- The first screen studied mitochondrial membrane potential (MMP) collapse in response to calcium overload, identifying MCU and EMRE as top-ranked genes.
- The second screen measured inner mitochondrial membrane permeability, identifying NF2, REST, BPTF, and NLRX1 as genes affecting mPT.
- NLRX1 knockout increased mitochondrial calcium retention capacity (CRC), abolished calcium release, and was cyclosporin A (CsA)-insensitive, meeting the definition of an essential mPT activator.
- Integral membrane proteins, including previously proposed mPT candidates, were not essential activators.