Tmbim5 and Slc8b1 cooperate in tissue-specific mitochondrial calcium regulation in zebrafish
Iga Wasilewska, Łukasz Majewski, Dobrochna Adamek-Urbańska, Sofiia Baranykova, Paulina Castañeda-Tamez, Ilka Wittig, Matylda Macias, Aleksandra Szybińska, Axel Methner
TL;DR
This study shows how Tmbim5 and Slc8b1 work together in zebrafish to control calcium in mitochondria, with different effects in brain and muscle tissues.
Contribution
The study reveals that Tmbim5 functions as an auxiliary calcium efflux pathway cooperating with Slc8b1 in a tissue-specific manner.
Findings
Tmbim5-deficient zebrafish showed growth impairment, muscle atrophy, and increased brain cell death.
Tmbim5 and Slc8b1 cooperate in mitochondrial calcium regulation with tissue-specific effects in brain and muscle.
Double knockouts of tmbim5/slc8b1 showed reduced calcium uptake and efflux with tissue-specific rescue and exacerbation of phenotypes.
Abstract
Mitochondrial calcium homeostasis involves coordinated uptake via the mitochondrial calcium uniporter (MCU) and efflux through sodium-dependent NCLX (encoded by SLC8B1) and/or TMEM65. We investigated TMBIM5, a proposed bidirectional mitochondrial calcium/proton transporter, by generating zebrafish lacking tmbim5, slc8b1, plus tmbim5/mcu and tmbim5/slc8b1 double knockouts. Tmbim5-deficient fish exhibited growth impairment, muscle atrophy, and increased brain cell death. tmbim5/mcu double knockouts showed no additive effects, arguing against Tmbim5 functioning as an independent calcium uptake pathway. slc8b1 knockouts had no major phenotype but showed attenuated, although not abolished sodium-dependent mitochondrial calcium efflux. tmbim5/slc8b1 double knockouts showed altered mitochondrial calcium handling with reduced uptake and efflux. Remarkably, brain phenotypes were rescued while…
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Taxonomy
TopicsMitochondrial Function and Pathology · Adipose Tissue and Metabolism · Calpain Protease Function and Regulation