Novel Drosophila model for mitochondrial diseases by targeting of a solute carrier protein SLC25A46

Suda, Kojiro; Ueoka, Ibuki; Azuma, Yumiko; Muraoka, Yuuka; Yoshida, Hideki; Yamaguchi, Masamitsu

doi:10.1016/j.brainres.2018.03.028

Cited by 20 publications

(13 citation statements)

References 37 publications

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“…Initially described in patients with an optic atrophy spectrum disorder (including axonal sensorimotor neuropathy) [143,144], SLC25A46 variants are also linked to Leigh syndrome [74], progressive myoclonic ataxia with neuropathy [145], cerebellar ataxia [146], pontocerebellar hypoplasia [147,148] and Parkinson Disease [149]. Several animal models, including mouse [150][151][152][153], zebrafish [143], and Drosophila [154], also have neurologic phenotypes that recapitulate human disease. In addition to altered cristae structure and impaired bioenergetics, these animal models show mitochondrial impairment with enlarged mitochondria that have abnormal distribution and which colocalize with the autophagy marker LC3B, consistent with impaired mitophagy.…”

Section: Slc25a46mentioning

confidence: 99%

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Sharma

Pfeffer

Shutt

2021

Biology

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Mitochondria are dynamic organelles capable of fusing, dividing, and moving about the cell. These properties are especially important in neurons, which in addition to high energy demand, have unique morphological properties with long axons. Notably, mitochondrial dysfunction causes a variety of neurological disorders including peripheral neuropathy, which is linked to impaired mitochondrial dynamics. Nonetheless, exactly why peripheral neurons are especially sensitive to impaired mitochondrial dynamics remains somewhat enigmatic. Although the prevailing view is that longer peripheral nerves are more sensitive to the loss of mitochondrial motility, this explanation is insufficient. Here, we review pathogenic variants in proteins mediating mitochondrial fusion, fission and transport that cause peripheral neuropathy. In addition to highlighting other dynamic processes that are impacted in peripheral neuropathies, we focus on impaired mitochondrial quality control as a potential unifying theme for why mitochondrial dysfunction and impairments in mitochondrial dynamics in particular cause peripheral neuropathy.

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Section: Slc25a46mentioning

confidence: 99%

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Sharma

Pfeffer

Shutt

2021

Biology

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“…The phenotypes induced by the knockdown of each dSLC25A46 gene seem to be very similar, suggesting that they might play non-superimposable roles in D. melanogaster , not complementing the defects induced by the knockdown of each other. Moreover, the subcellular localization of dSLC25A46b supports this hypothesis, since it localizes not only to mitochondria but also to the plasma membrane, where it could perform a different range of functions [ 250 ].…”

Section: Drosophila Melanogaster Vs Human Mitomentioning

confidence: 99%

“…In particular, locomotor impairment and defects in neuromuscular junctions compromising synaptic function were observed in mutant fruit flies at different developmental stages. The knockdown of dSLC25A46a or dSLC25A46b also led to severe structural and functional mitochondrial defects, at least in part associated with ROS accumulation and ATP level reductions [ 249 , 250 ].…”

Section: Drosophila Melanogaster Vs Human Mitomentioning

confidence: 99%

Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers

Curcio

Lunetti

Zara

et al. 2020

IJMS

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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.

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“…104,105 SLC25A46 (solute carrier family 25, member 46) can regulate MD and cristae maintenance by promoting mitochondrial fission and preventing the formation of mitochondrial hyperfilamentation. 106…”

Section: Fusion and Fission Coordinators In MDmentioning

confidence: 99%

Therapeutic potential and recent advances on targeting mitochondrial dynamics in cardiac hypertrophy: A concise review

Aung

Jumbo

Wang

et al. 2021

Molecular Therapy - Nucleic Acids

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Pathological cardiac hypertrophy begins as an adaptive response to increased workload; however, sustained hemodynamic stress will lead it to maladaptation and eventually cardiac failure. Mitochondria, being the powerhouse of the cells, can regulate cardiac hypertrophy in both adaptive and maladaptive phases; they are dynamic organelles that can adjust their number, size, and shape through a process called mitochondrial dynamics. Recently, several studies indicate that promoting mitochondrial fusion along with preventing mitochondrial fission could improve cardiac function during cardiac hypertrophy and avert its progression toward heart failure. However, some studies also indicate that either hyperfusion or hypo-fission could induce apoptosis and cardiac dysfunction. In this review, we summarize the recent knowledge regarding the effects of mitochondrial dynamics on the development and progression of cardiac hypertrophy with particular emphasis on the regulatory role of mitochondrial dynamics proteins through the genetic, epigenetic, and post-translational mechanisms, followed by discussing the novel therapeutic strategies targeting mitochondrial dynamic pathways. Box 1 FactsMitochondrial dynamics is directly linked to mitochondrial function and cellular homeostasis. When impaired, mitochondrial dynamics can influence a wide range of cellular processes, including mitochondrial biogenesis, energy metabolism, mtDNA maintenance, mitochondrial quality control, ROS production, Ca 2+ signaling, cell cycle and stem cell regulation, mitophagy, autophagy, and apoptosis.Increased mitochondrial fragmentation, decreased mitochondrial density, and increased apoptosis are detected in multiple forms of cardiomyopathy and heart failure. Upregulation of mitochondrial fission factors (Drp1 and Fis1) and downregulation of mitochondrial fusion proteins (Mfn1/2 and Opa1) underline the development of cardiac hypertrophy and progression toward heart failure. Drugs reducing mitochondrial fission show a significant diminution in cardiac hypertrophy and improvement in cardiac function. Box 2 Open questions How are mitochondrial dynamics and apoptosis regulated in the course of cardiac hypertrophy? What are the characteristic changes in mitochondrial morphology that determine cardiac hypertrophy? What are the potential side effects of long-term manipulation of mitochondrial dynamics in patients with cardiac hypertrophy?How can mitochondrial morphology be effectively detected in patients with cardiac hypertrophy?

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Novel Drosophila model for mitochondrial diseases by targeting of a solute carrier protein SLC25A46

Cited by 20 publications

References 37 publications

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers

Therapeutic potential and recent advances on targeting mitochondrial dynamics in cardiac hypertrophy: A concise review

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