SMDT1 variants impair EMRE-mediated mitochondrial calcium uptake in patients with muscle involvement.
Biochim Biophys Acta Mol Basis Dis
; 1869(8): 166808, 2023 12.
Article
in En
| MEDLINE
| ID: mdl-37454773
ABSTRACT
Ionic calcium (Ca2+) is a key messenger in signal transduction and its mitochondrial uptake plays an important role in cell physiology. This uptake is mediated by the mitochondrial Ca2+ uniporter (MCU), which is regulated by EMRE (essential MCU regulator) encoded by the SMDT1 (single-pass membrane protein with aspartate rich tail 1) gene. This work presents the genetic, clinical and cellular characterization of two patients harbouring SMDT1 variants and presenting with muscle problems. Analysis of patient fibroblasts and complementation experiments demonstrated that these variants lead to absence of EMRE protein, induce MCU subcomplex formation and impair mitochondrial Ca2+ uptake. However, the activity of oxidative phosphorylation enzymes, mitochondrial morphology and membrane potential, as well as routine/ATP-linked respiration were not affected. We hypothesize that the muscle-related symptoms in the SMDT1 patients result from aberrant mitochondrial Ca2+ uptake.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium Channels
/
Calcium
Limits:
Humans
Language:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
Year:
2023
Document type:
Article
Affiliation country:
Países Bajos