Cargando…
Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions
INDY (I’m Not Dead Yet) is a plasma membrane transporter for citrate, first identified in Drosophila. Partial deficiency of INDY extends lifespan in this organism in a manner similar to that of caloric restriction. The mammalian counterpart (NaCT/SLC13A5) also transports citrate. In mice, it is the...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537002/ https://www.ncbi.nlm.nih.gov/pubmed/34677384 http://dx.doi.org/10.3390/metabo11100669 |
_version_ | 1784588144053583872 |
---|---|
author | Jaramillo-Martinez, Valeria Sivaprakasam, Sathish Ganapathy, Vadivel Urbatsch, Ina L. |
author_facet | Jaramillo-Martinez, Valeria Sivaprakasam, Sathish Ganapathy, Vadivel Urbatsch, Ina L. |
author_sort | Jaramillo-Martinez, Valeria |
collection | PubMed |
description | INDY (I’m Not Dead Yet) is a plasma membrane transporter for citrate, first identified in Drosophila. Partial deficiency of INDY extends lifespan in this organism in a manner similar to that of caloric restriction. The mammalian counterpart (NaCT/SLC13A5) also transports citrate. In mice, it is the total, not partial, absence of the transporter that leads to a metabolic phenotype similar to that caloric restriction; however, there is evidence for subtle neurological dysfunction. Loss-of-function mutations in SLC13A5 (solute carrier gene family 13, member A5) occur in humans, causing a recessive disease, with severe clinical symptoms manifested by neonatal seizures and marked disruption in neurological development. Though both Drosophila INDY and mammalian INDY transport citrate, the translocation mechanism differs, the former being a dicarboxylate exchanger for the influx of citrate(2−) in exchange for other dicarboxylates, and the latter being a Na(+)-coupled uniporter for citrate(2−). Their structures also differ as evident from only ~35% identity in amino acid sequence and from theoretically modeled 3D structures. The varied biological consequences of INDY deficiency across species, with the beneficial effects predominating in lower organisms and detrimental effects overwhelming in higher organisms, are probably reflective of species-specific differences in tissue expression and also in relative contribution of extracellular citrate to metabolic pathways in different tissues |
format | Online Article Text |
id | pubmed-8537002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85370022021-10-24 Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions Jaramillo-Martinez, Valeria Sivaprakasam, Sathish Ganapathy, Vadivel Urbatsch, Ina L. Metabolites Review INDY (I’m Not Dead Yet) is a plasma membrane transporter for citrate, first identified in Drosophila. Partial deficiency of INDY extends lifespan in this organism in a manner similar to that of caloric restriction. The mammalian counterpart (NaCT/SLC13A5) also transports citrate. In mice, it is the total, not partial, absence of the transporter that leads to a metabolic phenotype similar to that caloric restriction; however, there is evidence for subtle neurological dysfunction. Loss-of-function mutations in SLC13A5 (solute carrier gene family 13, member A5) occur in humans, causing a recessive disease, with severe clinical symptoms manifested by neonatal seizures and marked disruption in neurological development. Though both Drosophila INDY and mammalian INDY transport citrate, the translocation mechanism differs, the former being a dicarboxylate exchanger for the influx of citrate(2−) in exchange for other dicarboxylates, and the latter being a Na(+)-coupled uniporter for citrate(2−). Their structures also differ as evident from only ~35% identity in amino acid sequence and from theoretically modeled 3D structures. The varied biological consequences of INDY deficiency across species, with the beneficial effects predominating in lower organisms and detrimental effects overwhelming in higher organisms, are probably reflective of species-specific differences in tissue expression and also in relative contribution of extracellular citrate to metabolic pathways in different tissues MDPI 2021-09-29 /pmc/articles/PMC8537002/ /pubmed/34677384 http://dx.doi.org/10.3390/metabo11100669 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Jaramillo-Martinez, Valeria Sivaprakasam, Sathish Ganapathy, Vadivel Urbatsch, Ina L. Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions |
title | Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions |
title_full | Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions |
title_fullStr | Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions |
title_full_unstemmed | Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions |
title_short | Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions |
title_sort | drosophila indy and mammalian indy: major differences in transport mechanism and structural features despite mostly similar biological functions |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537002/ https://www.ncbi.nlm.nih.gov/pubmed/34677384 http://dx.doi.org/10.3390/metabo11100669 |
work_keys_str_mv | AT jaramillomartinezvaleria drosophilaindyandmammalianindymajordifferencesintransportmechanismandstructuralfeaturesdespitemostlysimilarbiologicalfunctions AT sivaprakasamsathish drosophilaindyandmammalianindymajordifferencesintransportmechanismandstructuralfeaturesdespitemostlysimilarbiologicalfunctions AT ganapathyvadivel drosophilaindyandmammalianindymajordifferencesintransportmechanismandstructuralfeaturesdespitemostlysimilarbiologicalfunctions AT urbatschinal drosophilaindyandmammalianindymajordifferencesintransportmechanismandstructuralfeaturesdespitemostlysimilarbiologicalfunctions |