2020
DOI: 10.1101/2020.02.06.937920
|View full text |Cite
Preprint
|
Sign up to set email alerts
|

The TIM22 complex regulates mitochondrial one-carbon metabolism by mediating the import of Sideroflexins

Abstract: words)The Acylglycerol Kinase (AGK) is a mitochondrial lipid kinase that contributes to protein biogenesis as a subunit of the TIM22 complex at the inner mitochondrial membrane. Mutations inAGK cause Sengers syndrome, an autosomal recessive condition characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. We undertook proteomic profiling of Sengers patient fibroblasts and an AGKKO cell line to map the proteomic changes that ensue upon AGK dysfunction. This unc… Show more

Help me understand this report
View published versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

3
8
0

Year Published

2020
2020
2022
2022

Publication Types

Select...
3
2

Relationship

0
5

Authors

Journals

citations
Cited by 7 publications
(11 citation statements)
references
References 40 publications
(63 reference statements)
3
8
0
Order By: Relevance
“…However, recent work has identified the mitochondrial pyruvate carrier proteins with their divergent topology as substrates of the TIM22 pathway [ 31 , 32 ]. What is more, the unrelated sideroflexins also rely on the TIM22 carrier translocase for their biogenesis [ 38 , 39 ]. Of the MPC components, at least Mpc2 and Mpc3 have unpaired TM helices and none of the MPC proteins possess more than three TM segments [ 6 , 7 , 35 , 36 , 37 ], while the sideroflexins also have an uneven number of TM segments and yet another topology [ 8 , 39 ] ( Figure 2 ).…”
Section: Membrane Integration By the Tim22 Carrier Translocasementioning
confidence: 99%
See 3 more Smart Citations
“…However, recent work has identified the mitochondrial pyruvate carrier proteins with their divergent topology as substrates of the TIM22 pathway [ 31 , 32 ]. What is more, the unrelated sideroflexins also rely on the TIM22 carrier translocase for their biogenesis [ 38 , 39 ]. Of the MPC components, at least Mpc2 and Mpc3 have unpaired TM helices and none of the MPC proteins possess more than three TM segments [ 6 , 7 , 35 , 36 , 37 ], while the sideroflexins also have an uneven number of TM segments and yet another topology [ 8 , 39 ] ( Figure 2 ).…”
Section: Membrane Integration By the Tim22 Carrier Translocasementioning
confidence: 99%
“…For the human TIM22 translocase a differential requirement of the auxiliary subunits for different substrate classes has been reported: AGK is required for efficient carrier import and dispensable for the import of Tim22 and related proteins [ 103 , 104 ], whereas the opposite is the case for Tim29 [ 92 ]. Interestingly, sideroflexins, like classical carriers, rely on AGK, while Tim29 is dispensable [ 38 ]. It will be very interesting to learn how TIM22 adapts its function to import this range of structurally distinct substrates.…”
Section: Membrane Integration By the Tim22 Carrier Translocasementioning
confidence: 99%
See 2 more Smart Citations
“…SLC56A3/SFXN3 and SLC56A2/SFXN2 can compensate for this function, as well as yeast and Drosophila homologues, indicating an ancestral function, while SLC56A4/SFXN4 and SLC56A5/SFXN5 were unable to do so, indicating a possible altered transport rate or substrate selectivity [54]. Regarding their mitochondrial targeting, sideroflexins do not show any canonical MTS [53], and instead are targeted to the mitochondria via the TIM22 import complex [55][56][57], similarly to SLC25 proteins. Very little is currently known about the structure and function of sideroflexin transporters.…”
Section: Slc56-sideroflexinsmentioning
confidence: 99%