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

Joseph A Bonanno; Raji Shyam; Moonjung Choi; Diego G Ogando

doi:10.3390/cells11020197

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

Journal article

Open access

Peer reviewed

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

Joseph A Bonanno, Raji Shyam, Moonjung Choi and Diego G Ogando

Cells (Basel, Switzerland), Vol.11(2), p.197

01/07/2022

DOI: 10.3390/cells11020197

PMCID: PMC8773465

PMID: 35053313

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Abstract

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.

Animals

Anion Transport Proteins - genetics

Anion Transport Proteins - metabolism

Gene Expression Regulation

Genetic Predisposition to Disease

Humans

Mitochondria - metabolism

Oxidative Stress - genetics

Protons

Details

Title: Subtitle: The H + Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling
Creators: Joseph A Bonanno - Indiana University Bloomington
Raji Shyam - Indiana University Bloomington
Moonjung Choi - Indiana University Bloomington
Diego G Ogando - Indiana University Bloomington
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.11(2), p.197
DOI: 10.3390/cells11020197
PMID: 35053313
PMCID: PMC8773465
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Grant note: R01 EY008834 / NEI NIH HHS R01 EY031321 / NEI NIH HHS 5R01EY031321 / NIH HHS
Language: English
Date published: 01/07/2022
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984949264502771

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