Criticality of the Phosphate Carrier SLC25A3 for Mitochondrial Inorganic Phosphate Uptake to Sustain Striated Muscle Function

reportActive / Technical Report | Accesssion Number: AD1211993 | Open PDF

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.

Author(s):
Seifert, Erin
Author Organization(s):
THOMAS JEFFERSON UNIV PHILADELPHIA PA
Funding Organization(s):
ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND FORT DETRICK MD, FORT DETRICK, MD
Document Type:
Technical Report/Final Report
Publication Date:
2022 Jan 01
Pagination:
70

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DOCUMENT & CONTEXTUAL SUMMARY

Distribution Code:
A - Approved For Public Release
Distribution Statement: Public Release.
Copyright: Not Copyrighted

RECORD

Collection: TRECMS
Subject Terms
Descriptor(s):
medical personnel, chemistry, cells, mitochondria, skeletal muscle, metabolic diseases, intracellular membranes, cellular structures, connective tissue, subcellular fractions, animal structures, cell line, cell membrane, muscular diseases, striated muscle, cultured cells
Keyword(s):
Inorganic phosphate, Mitochondrial inner membrane transporters, Oxidative phosphorylation, Mitochondrial calcium uptake, TAT fusion protein, Mitochondrial myopathy, Mitochondrial disease, Nutrient signaling in skeletal muscle
Subject Categories:
Biological and Medical Sciences
Descriptor(s):
chemistry, cells, mitochondria, skeletal muscle, intracellular membranes, metabolic diseases, cellular structures, connective tissue, subcellular fractions, animal structures, cell line, cell membrane, muscular diseases, striated muscle, cultured cells, muscle cells
Creation Date:
2023 Oct 02
Update Date:
2023 Nov 13