Abstract

Mitochondrial carriers are a family of structurally related proteins responsible for the exchange of metabolites, cofactors and nucleotides between the cytoplasm and mitochondrial matrix. The in silico analysis of the Drosophila melanogaster genome has highlighted the presence of 48 genes encoding putative mitochondrial carriers, but only 20 have been functionally characterized. Despite most Drosophila mitochondrial carrier genes having human homologs and sharing with them 50% or higher sequence identity, D. melanogaster genes display peculiar differences from their human counterparts: (1) in the fruit fly, many genes encode more transcript isoforms or are duplicated, resulting in the presence of numerous subfamilies in the genome; (2) the expression of the energy-producing genes in D. melanogaster is coordinated from a motif known as Nuclear Respiratory Gene (NRG), a palindromic 8-bp sequence; (3) fruit-fly duplicated genes encoding mitochondrial carriers show a testis-biased expression pattern, probably in order to keep a duplicate copy in the genome. Here, we review the main features, biological activities and role in the metabolism of the D. melanogaster mitochondrial carriers characterized to date, highlighting similarities and differences with their human counterparts. Such knowledge is very important for obtaining an integrated view of mitochondrial function in D. melanogaster metabolism.

Highlights

  • Drosophila melanogaster, commonly known as the fruit fly, is a useful model organism for studies on aging

  • When starvation was prolonged, the UCP5KO flies depleted their reserves more rapidly and died faster than controls [142]. With these findings, and considering that ectopic neuronal DmUCP5 expression was able restore starvation resistance in UCP5KO flies, this carrier could be involved in the control of metabolic homeostasis at the brain level, by uncoupling mitochondria in brain neurosecretory cells and affecting their secretion of adipokinetic hormone and insulin-like peptides [143]

  • Mitochondrial carriers are membrane proteins transporting across mitochondria many different metabolites, which are involved in several biochemical pathways, including energetic metabolism, hormonal metabolic homeostasis, cell survival, proliferation and protection from oxidative stress, among many others

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Summary

Introduction

Drosophila melanogaster, commonly known as the fruit fly, is a useful model organism for studies on aging. It is relatively easy to culture, has a conveniently short lifespan, consists of mostly post-mitotic tissues (except for the reproductive system and a small part of the gut), and has a fully sequenced genome and well-characterized genetics This insect uses many mitochondrial transporters homologous to the human carriers, as well as the same mechanisms for transporting several metabolites from cytosol to mitochondria and vice versa. Mitochondrial carriers are essential in many biochemical processes, such as the citric acid cycle, oxidative phosphorylation, the transfer of NADH and NADPH reducing equivalents, gluconeogenesis, and amino acid and fatty acid metabolism, as well as in mitochondrial duplication, transcription and translation processes, calcium-mediated cell signaling pathways and insulin secretion [1,2,3] The existence of these carriers was demonstrated in the 1970s by transport studies carried out firstly on intact mitochondria [4] and using artificial membranes (liposomes), in which individual isolated and purified proteins were functionally reconstituted [5]. Intra- and inter-genome comparisons have allowed a first assessment of the evolution of this protein family

The Citrate Carrier
The Uncoupling Proteins
The Dicarboxylate Carriers
The Glutamate Carrier
The Thiamine Pyrophosphate Carrier
The Mitoferrin
2.10. The Shawn Protein
2.11. Dephosphocoenzyme A Carrier
Findings
Conclusions
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