Pathogenic variants of the mitochondrial aspartate/glutamate carrier causing citrin deficiency

Sotiria Tavoulari, Denis Lacabanne, Chancievan Thangaratnarajah, Edmund R S Kunji*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

32 Citations (Scopus)
177 Downloads (Pure)

Abstract

Citrin deficiency is a pan-ethnic and highly prevalent mitochondrial disease with three different stages: neonatal intrahepatic cholestasis (NICCD), a relatively mild adaptation stage, and type II citrullinemia in adulthood (CTLN2). The cause is the absence or dysfunction of the calcium-regulated mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also called citrin, which imports glutamate into the mitochondrial matrix and exports aspartate to the cytosol. In citrin deficiency, these missing transport steps lead to impairment of the malate-aspartate shuttle, gluconeogenesis, amino acid homeostasis, and the urea cycle. In this review, we describe the geological spread and occurrence of citrin deficiency, the metabolic consequences and use our current knowledge of the structure to predict the impact of the known pathogenic mutations on the calcium-regulatory and transport mechanism of citrin.

Original languageEnglish
Pages (from-to)539-553
Number of pages15
JournalTrends in endocrinology and metabolism
Volume33
Issue number8
DOIs
Publication statusPublished - Aug-2022

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  • oLife Fellowship Programme

    Roos, W. (PI), van der Tak, F. (PI), Zijlstra, W. (PI), Dobos, V. (Postdoc), Heinen, L. (Postdoc), Thangaratnarajah, C. (Postdoc), Hoekzema, M. (Postdoc), Blokhuis, A. (Postdoc), Mascotti, L. (Postdoc), Padin Santos, D. (Postdoc), Chopra, A. (Postdoc), Obermaier, S. (Postdoc), Driver, M. (Postdoc), Moreira Goulart, M. (Postdoc), Sasidharan, S. (Postdoc), Samar Mahapatra, S. (Postdoc), Zylstra, A. (Postdoc), Geiger, Y. (Postdoc), Llopis Lorente, A. (Postdoc), Aschmann, D. (Postdoc) & Kulala Vittala, S. (Postdoc)

    01/04/201931/03/2024

    Project: Research

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