Dystonia and Hereditary Motor Sensory Neuropathy <scp>6B</scp> Due to <scp><i>SLC25A46</i></scp> Gene Mutations

Raju, S. P. Govinda; Medarametla, Soumya; Boraiah, Nataraju

doi:10.1002/mdc3.13139

Cited by 7 publications

(2 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SLC25A46 interacts with both fusion GTPases and has emerged as an intermembrane bridging protein which plays roles in regulating mitochondrial membrane dynamics (6)(7)(8)(9). Mutations in SLC25A46 result in optic atrophy spectrum disorder, Leigh syndrome, and pontocerebellar hypoplasia (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). SLC25A46 is a member of the solute carrier family 25 of mitochondrial transporters, which transport substrates such as nucleotides, vitamins, amino acids, fatty acids across the inner mitochondrial membrane (IMM) (25).…”

Section: Introductionmentioning

confidence: 99%

“…Residing in the outer mitochondrial membrane (OMM), SLC25A46 lacks the signature sequence motifs of the SLC25 family (10), does not have an identified substrate and contains a distinct Nterminal extension. Mutations in SLC25A46 result in optic atrophy spectrum disorder, Leigh syndrome and pontocerebellar hypoplasia (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of SLC25A46 interaction interfaces with mitochondrial membrane fusogens Opa1 and Mfn2

Boopathy,

Luce,

Lugo

et al. 2023

Preprint

View full text Add to dashboard Cite

Mitochondrial fusion requires the sequential merger of four bilayers to two. The outer-membrane solute carrier protein SLC25A46 interacts with both the outer and inner-membrane dynamin family GTPases Mfn1/2 and Opa1. While SLC25A46 levels are known affect mitochondrial morphology, how SLC25A46 interacts with Mfn1/2 and Opa1 to regulate membrane fusion is not understood. In this study, we use crosslinking mass-spectrometry and AlphaFold 2 modeling to identify interfaces mediating a SLC25A46-Opa1-Mfn1/2 complex. We reveal that the bundle signaling element of Opa1 interacts with SLC25A46, and the helical repeat 1 region of Mfn2 interacts with the SLC25A46 N-terminus. We validate these newly identified interaction interfaces and show that they play a role in mitochondrial network maintenance.

show abstract