Penna 2016 Abstract Mito Xmas Meeting Innsbruck

Impact of CCDC90B on mitochondrial functions.

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Penna E, De Stefani D, Rizzuto R (2016)

Event: Mito Xmas Meeting 2016 Innsbruck AT

Mitochondria are the masters of cellular energy metabolism and are crucially involved in a number of metabolic and signal transduction pathways. Several pathological conditions are associated with dysfunction of the oxidative phosphorylation (OXPHOS), impairment of the Electron Transport Chain (ETC) and ROS production. In this work we investigated the role of an uncharacterized mitochondrial protein named CCDC90B. CCDC90B is ubiquitously expressed and broadly conserved until yeasts. Its ortholog in S. cerevisiae encodes for a protein called FMP32, recently described as an assembly factor for cytochrome c oxidase (COX) [1]. However, in mammals an additional isoform named CCDC90A is present and has been recently described to regulate mitochondrial Ca2+ uptake (and hence it is also known as MCUR1) [2]. Here we investigate how CCDC90B impacts on both OXPHOS and organelle calcium handling in human cells. We demonstrated that CCDC90B can physically interact with its isoform CCDC90A. However, we didn’t detect any major functional interaction with all the known members of the Mitochondrial Calcium Uniporter (MCU) complex, although the downregulation of CCDC90B causes a defective organelle Ca2+ uptake. Most importantly, we found that both silencing and ablation of CCDC90B decrease mitochondrial membrane potential and O2 consumption rate (OCR). Overall, this work describes a novel mitochondrial protein that, unlikely its closely related isoform, it plays no direct role in the regulation of mitochondrial Ca2+ uptake but rather controls the activity of the ETC.

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Event: Poster 

Affiliations

Penna E, De Stefani D, Rizzuto R

1. Dept Biomedical Sc, Univ Padua, Italy

Reference

1. Paupe, V., et al., CCDC90A (MCUR1) Is a Cytochrome c Oxidase Assembly Factor and Not a Regulator
of the Mitochondrial Calcium Uniporter . Cell Metabolism, 2015. 21: p. 109–116.
2. Mallilankaraman, K., et al., MCUR1 is an essential component of mitochondrial Ca(2+) uptake that regulates cellular metabolism. Nat Cell Biol, 2012. 14(12): p. 1336-43.