The H + Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling

Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H transporter activated by NH and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corn...

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Bibliographic Details
Published in:	Cells (Basel, Switzerland) Vol. 11; no. 2; p. 197
Main Authors:	Bonanno, Joseph A, Shyam, Raji, Choi, Moonjung, Ogando, Diego G
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 07-01-2022 MDPI
Subjects:	Amino acids Ammonia Animals Anion Transport Proteins - genetics Anion Transport Proteins - metabolism Antioxidants Autophagy Bicarbonates Cochlea Cornea corneal endothelial dystrophy Dystrophy Edema Endothelium Gene Expression Regulation Genetic Predisposition to Disease Glutamine Humans Hydrogen Hyperpolarization Kidneys lactate Localization Lysosomes MCT4 Membrane potential Mitochondria Mitochondria - metabolism Mutation Oxidative metabolism Oxidative stress Oxidative Stress - genetics Physiology Plasma Polyuria Proteins Protons Review Salivary gland Stem cells ammonia MCT4 glutamine lactate corneal endothelial dystrophy
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Summary:	Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H transporter activated by NH and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes. Outside of the corneal endothelium, SLC4A11's function has been demonstrated in cochlear fibrocytes, salivary glands, and kidneys, but is largely unexplored overall. Increased SLC4A11 expression is a component of some "glutamine-addicted" cancers, and is possibly linked to cells and tissues that rely on glutamine catabolism.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-2
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells11020197