Criticality of the Phosphate Carrier SLC25A3 for Mitochondrial Inorganic Phosphate Uptake to Sustain Striated Muscle Function
Abstract
This project investigates the criticality of the mitochondrial phosphate carrier (PiC) for oxidative phosphorylation (oxphos; Aim 1) and buffering of mitochondrial matrix Ca2+ (Aim 2). Aim 3 focuses on the generation of TAT fusion proteins for the PiC and their ability to rescue phenotypes induced by PiC depletion. In this reporting period (Nov 2020 Oct 2021), substantial progress was made on Aims 2 and 3. For Aim 2, we have almost completed a manuscript that investigates the role of the PiC in mitochondrial Ca2+ handling and the implications on cytosolic Ca2+ signaling in muscle fibers and force generation of intact muscle. These studies utilized a new mouse model in which PiC is deleted specifically in skeletal muscle (skm), in a Tamoxifen-inducible fashion. For the experiments, PiC was deleted by injecting 9-week old mice with Tamoxifen; skm mitochondria, intact fibers and whole muscle were harvested 2 weeks later at which point PiC protein was only ~5-10% of normal levels.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1211993
Entities
People
- Erin L Seifert
Organizations
- Thomas Jefferson University