respiratory complex assembly/ respirasome assembly

ValWood commented 1 month ago

Systematic ID	Gene name	Product description	Budding yeast orthologs	Human orthologs	Targets
SPBC115.02c	afg1	AFG1 family mitochondrial ATPase/chaperone Afg1	AFG1	AFG1L
SPBC21D10.07	cmc1	copper-binding protein of the mitochondrial intermembrane space Cmc1	CMC1,CMC2	CMC1,CMC2
SPBC16E9.03c	coa1	cytochrome c oxidase assembly protein Coa1	COA1	COA1
SPAC15A10.17	coa2	cytochrome c oxidase assembly protein Coa2	COA2	NDUFA3
SPAC1B3.21	coa3	cytochrome c oxidase assembly protein Coa3	COA3	COA3
SPCC550.01c	coa4	cytochrome c oxidase assembly protein Coa4	COA4	COA4
SPBC16A3.16	coa5	cytochrome c oxidase assembly protein Coa5	PET191	COA5
SPBC24C6.13	coa6	cytochrome c oxidase assembly protein Coa6	COA6	COA6
SPAC1420.04c	cox1101	cytochrome c oxidase assembly protein Cox1101/ mitochondrial ribosome assembly protein Rsm22 fusion protein	COX11,RSM22	COX11,METTL17
SPAC19B12.13	cox1102	cytochrome c oxidase assembly protein Cox1102/ mitochondrial ribosome assembly protein Rsm2202, fusion protein	COX11,RSM22	COX11,METTL17
SPCC757.15	cox14	cytochrome c oxidase assembly protein Cox14	COX14	COX14
SPBC25H2.18	cox20	cytochrome c oxidase assembly protein Cox20	COX20	COX20
SPBC1604.25	pet117	cytochrome c oxidase assembly protein Pet117	PET117	PET117
SPAC25B8.07c	rcf1	cytochrome c oxidase assembly protein Rcf1	RCF1	HIGD1A,HIGD1B,HIGD1C,HIGD2A,HIGD2B
SPBC1215.01	shy1	cytochrome c oxidase assembly protein Shy1	SHY1	SURF1
SPCC4B3.20	cmc2	cytochrome c oxidase assembly protein, copper-binding, Cmc2	CMC1,CMC2	CMC1,CMC2
SPAC1565.01	rcf2	cytochrome c oxidase subunit Rcf2	RCF2	HIGD1A,HIGD1B,HIGD1C,HIGD2A,HIGD2B
SPAC2C4.09		mitochondrial calcium uniporter regulator	FMP32	CCDC90B,MCUR1
SPAC3H1.08c		mitochondrial calcium uniporter regulator	FMP32	CCDC90B,MCUR1
SPBC947.14c	cbp6	mitochondrial complex III assembly protein Cbp6	CBP6	UQCC2
SPAC1486.08	cox16	mitochondrial copper chaperone for cytochrome c oxidase Cox16	COX16	COX16
SPBC26H8.14c	cox17	mitochondrial copper chaperone for cytochrome c oxidase Cox17	COX17	COX17
SPCC1672.04c	cox19	mitochondrial copper chaperone for cytochrome c oxidase Cox19	COX19	COX19
SPBC119.06	sco1	mitochondrial copper chaperone for cytochrome c oxidase Sco1	SCO1,SCO2	SCO1,SCO2
SPAC25B8.04c	mss51	mitochondrial cytochrome C oxidase assembly protein Mss51	MSS51	MSS51
SPAC4G8.11c	atp10	mitochondrial F1-FO ATP synthase chaperone Atp10	ATP10
SPAC3A12.12	atp11	mitochondrial F1-FO ATP synthase chaperone Atp11	ATP11	ATPAF1
SPAC9.12c	atp12	mitochondrial F1-FO ATP synthase chaperone Atp12	ATP12	ATPAF2
SPBC3B8.10	ina17	mitochondrial F1-FO ATP synthase peripheral stalk assembly factor Ina17	INA17
SPAC926.10	ina22	mitochondrial F1-FO ATP synthase peripheral stalk assembly factor Ina22	INA22
SPCC1442.15c	cox18	mitochondrial inner membrane insertase Cox18	COX18	COX18
SPCC320.12	atp23	mitochondrial inner membrane peptidase Atp23	ATP23	ATP23
SPAC1486.11	fmc1	mitochondrial proton-transporting ATP synthase complex assembly factor, LYR family, Fmc1	FMC1	FMC1
SPAC1834.10c		mitochondrial proton-transporting ATP synthase complex assembly protein		TMEM70
SPAC25A8.03c		mitochondrial repliratory complex assembly factro/arginine methyltransferase, human NDUFAF7 ortholog	YKL162C	NDUFAF7
SPBC26H8.16	sdh8	mitochondrial respiratory chain complex II assembly factor 4 Sdh8	SDH8	SDHAF4	sdh1 (chaperone)
SPCC4B3.17	cbp3	mitochondrial respiratory chain complex III assembly protein Cbp3	CBP3	UQCC1
SPBC30D10.21	mzm1	mitochondrial respiratory chain complex III assembly protein, LYR family Mzm1	MZM1	LYRM7
SPBC27B12.14	cbp4	mitochondrial respiratory complex III assembly protein Cbp4	CBP4	UQCC3
SPBC3H7.08c	mra2	mitochondrial respiratory complex/ ATP synthase assembly protein Mra2	MRA1	C15orf48,NDUFA4,NDUFA4L2
SPAPB8E5.10	min8	mitochondrial respiratory complex/ATP synthase complex assembly protein Mra1, meiosis specific splicing in fission yeast	MRA1	C15orf48,NDUFA4,NDUFA4L2
SPAC644.07	bcs1	mitochondrial Rieske ISP assembly ATPase Bcs1	BCS1	BCS1L
SPAC664.12c	sdh6	mitochondrial succinate dehydrogenase assembly factor, LYR family Sdh6	SDH6	SDHAF1	sdh2
SPBP23A10.03c	sdh7	mitochondrial respiratory chain complex II assembly LYR family protein Sdh7	SDH7	SDHAF3	sdh2
SPAC12B10.06c	emi5	succinate dehydrogenase complex assembly protein Emi5	SDH5	SDHAF2
SPBC26H8.01	thi2	thiazole biosynthetic enzyme	THI4

hattrill commented 1 month ago

This is great. I have a rough but incomplete list of assembly factors. I will start putting them in some order. The HGNC have a list, if you want to check it against the human orthos: https://www.genenames.org/data/genegroup/#!/group/645

ValWood commented 1 month ago

need to deal with this too, is it a transferase? (flavination sounds like an activity)

hattrill commented 4 weeks ago

Google Doc for Assembly Factors

Orthologs via DIOPT. Best calls (Generally best hit in both directions, best scoring and score >3; except where noted) List from GO query of fly annotations, HGNC gene group Mitochondrial respiratory chain complex assembly factors , FlytoCarta list -> Human orthologs -> MitoCarta classification and additional query of list against FB gene groups for any revelant information. 3 genes added that are orthologous to Pombe gene list and not on this set.

Nest step to compare this to general reviews and verifiy/exclude genes.

Would be good to clarify the role of 'accessory' or 'supernumerary' respiratory complex subunits in assembly.

Also, need to think about what is meant by 'mitochondrial respirasome assembly'

ValWood commented 4 weeks ago

Notes

anything which is an LRR repeat protein is upstream of assembly. These are all involved in various aspects of gene expression (transcription, translation and splicing), but historically got annotated to complex assembly because the complexes don't for. I see a few of those in there.
also cox10 protoheme IX farnesyltransferase, catalyzes conversion of protoheme to heme A in heme A, so its required upstream of cyc1, cox1, cyt1 and tim18 (all have heme centres), was originally isolated as an assembly defect in cerevisiae
- would need to connect up from the ends of this pathway (same applies to etp1) https://amigo.geneontology.org/amigo/model/66c7d41500000841 depending on whether heme b,o, or a
There do appear to be genes specifically involved in the assembly of supercomplexes (aka respirasomes) i.e The levels of supercomplexes III2IV2 and III2IV were found to be lower in ∆shy1 cells compared to WT cells, while the abundance of COA complexes increased (Fig. 7a), indicating that the formation of supercomplexes involving complex IV is influenced by deletion of shy1. In contrast, the abundance of III2 and V complexes was largely unchanged in ∆shy1 cells (Fig. 7a).
UQCRB is ubiquinol-cytochrome-c reductase complex subunit 6 (so a respiratory complex III subunit rather than an assembly factor)
TACO1 is a translational activator, I plan to include in this it in this model http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A67086be200000519
TIMM21 upstream, import into matrix
respiratory chain complex IV

ValWood commented 4 weeks ago

@hattrill should "NOT SEEN" be in the final column for the ones below NDUFAB1 (I am assuming this always means that it isn't in my list?)

hattrill commented 4 weeks ago

Hi @ValWood there are quite a few that I have doubts about - some are modifiers and protein maturation factors that have made their way onto HGNC, MitoCarta or via GO - IBA, ISS, etc. As this is a mash-up of HGNC calls, MitoCarta calls and what we have in the GO, think there will be a lot of removal from this.

We have COX6B1 as a MITOCHONDRIAL COMPLEX IV - SUPERNUMERARY SUBUNIT gene groups. - I've made a note about those as many of the supernumerary/accessory subunits have assembly GO terms - I think that this is because they are required for complex stability rather than assembly and it's 'cellular phenotype that's been annotated. That's why need to align it against reviews.

"NOT SEEN" means that I found an ortholog via DIOPT for Pombe but not on your list (or I could have missed when I did the cross-search.

Human ATPSCKMT, FDXR, FDX2, HCCS, LRPPRC, OXA1L, SCO1 - come from HGNC or MitoCarta are ones on my current 'dump' list as they seem upstream to assembly.

ValWood commented 4 weeks ago

"NOT SEEN" means that I found an ortholog via DIOPT for Pombe but not on your list (or I could have missed when I did the cross-search.

I think this is sometimes in the wrong column

hattrill commented 4 weeks ago

Might have munged the formating - let me update it.

hattrill commented 4 weeks ago

Hopefully fixed now - some columns got merged a messed the layout up.

I will be removing a lot from the list....just trying to work out where to start - think that ones that are classed as accessory/supernumerary subunits will be first stop there are a lot.

ValWood commented 4 weeks ago

OK once you have cleaned up, I'll review the pombe ones and make sure all of mine are in your table. I have some definite orthologs for some: COA2 is SPBC16E9.03c(coa2) TTC19 is SPAP27G11.02(mgr3) equivalent complex member FMC1 is SPAC1486.11(fmc1) AIFM1 is SPAC26F1.14c(aif1) SAMM50 is SPAC17C9.06(sam50) pombe has no NDUFA2 (the human ortholog of pombe mrpl51 is human MRPL51) So I will add these (with the evidence once I dig it out).

I'll also have a good look for anything that is missing from pombe (although I am not expecting to find the Complex I assembly - because we don't have it). We do have 3 (I think ) of the subunits but these might really be assembly factors that are also used by other complexes (or something like that).

hattrill commented 4 weeks ago

This looks like a nice review publication to start with for me: https://doi.org/10.1042/EBC20170098....complex I assembly looks fun! Starting to wish we had no complex I ;-)

ValWood commented 4 weeks ago

The Wikipedia page isn't half bad, I was looking at it the other week when I found some of the assembly factors in pombe https://en.wikipedia.org/wiki/Respiratory_complex_I

hattrill commented 4 weeks ago

This is great - I woke up last night thinking I need to find a review with a table - this will do nicely!

ValWood commented 4 weeks ago

The things which keep us awake ! ;)

hattrill commented 4 weeks ago

Think I've found the paper that 'poisoned' the complex I assembly well - A lot of annotations originate from PMID:27626371 in which the KO of different accessory CI SUs were examined for their role in assembly. However, although the absence of SUs may impact assembly, I think that this is because they have a structural role in the complex/complex intermediates rather than being factors that assist in the assembly of the complex.

I like this as a definition of assembly "This multistep process involves transiently associated assembly factors that integrate core and accessory/supernumerary subunits as well as cofactors into the final holoenzyme." (PMID: 38086790).

I will have a bit more of a dig and then ask Alex Whitworth as if this works need to get a few places to revise their lists as well as GO.

hattrill commented 2 weeks ago

Think that list is ok now - will take a bit for GO fixes to filter down. (validating that no orthologs in Pombe for CI assembly factors) (Editted to remove COX7AL and COX7AL2. COX7AL is a CIV subunit and COX7AL2 is more similar to mammalian COX7A1 than COX7AL2, so more likely to be CIV SU.) (Editted (again) to add Tmem70 to the Complex I assembly factors (is also a complex V assembly factor, so duplicated lines). Reference for human PMID: 32275929. Also seen in a CI fly paper (PMID: 34386730), so feel confident adding.

ValWood commented 2 weeks ago

We do have bona fida orthologs of

COA1 (coa1 https://www.pombase.org/gene/SPBC16E9.03c

NDUFAF1 https://www.pombase.org/gene/SPAC9E9.15

TTC19 https://www.pombase.org/gene/SPAP27G11.02

[x] TMEM223 SPBP22H7.04 https://www.pombase.org/gene/SPBP22H7.04 evidence https://www.ebi.ac.uk/interpro/entry/pfam/PF06979/

These don't get picked up by the ortholog predictors but are clear from directed searches using Jackhmmer/FoldSeek/Pfam-N etc I will look for the other missing ones but Jackhmmer has been temporarily decommissioned by EBI

hattrill commented 2 weeks ago

That's good to know - I will add them. Some of these small things are hard to track down.

ValWood commented 2 weeks ago

Yes I'll also change for the pombe gene names (or add). Most name aren't in UniProt yet cos they don't do pombe

hattrill commented 2 weeks ago

Also, looks like we don't have an ortholog for SDHAF1 (Human), which is SPAC664.12c in Pombe

ValWood commented 2 weeks ago

The COA1 rows are duplicated (2 identical pairs under complex 1 and cytochrome c assembly)

hattrill commented 2 weeks ago

Yes, that's intentional as I am trying to keep it 1:1 with the term without using "|" - I also have 2 orthlogs for COA1 its a DUPLICATE X PARALOG situation!

hattrill commented 2 weeks ago

Can I ask you about afg1? Not so sure that it is an assembly factor, so left it off the list. Seems to be involved with protein turn-over or even import from these papers:

'The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1) mediates degradation of nuclear-encoded complex IV subunits' and Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase that shows a role in the degradation of some complex IV subunits And 'LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis' shows a role in apoptosis.

ValWood commented 2 weeks ago

FIXES

[x] PomBAse afg1 mitochondrial cytochrome c oxidase assembly NAS deleted
[x] UniProtKB:Q8WV93 | AFG1L GO:0006123 mitochondrial electron transport, cytochrome c to oxygen looks indirect disputed by helen =>"GO:0141164 mitochondrial protein quality control"
[x] PomBAse thi2 | GO:0033108 | mitochondrial respiratory chain complex assembly | ISO with S000003376 deleted

hattrill commented 2 weeks ago

[ ] UniProtKB:Q8WV93 | AFG1L GO:0006123 mitochondrial electron transport, cytochrome c to oxygen looks indirect

I've sent a dispute about this one yesterday as it is just wrong

ValWood commented 2 weeks ago

Woah, https://www.uniprot.org/uniprotkb/Q96E52/entry is over-annotated did you query any of the others?

CC @Antonialock

hattrill commented 2 weeks ago

Disputed some assembly annotations to human ones...and a special request for a big batch from PMID:27626371

hattrill commented 2 weeks ago

Looks like PMID:27626371 has been fixed :-)

hattrill commented 1 week ago

Do you think mss51 should be cytochrome c oxidase assembly factor or upstream of it - I am not sure. Could model it either way depending - in this fig they make it a preassembly step.

~Don't have a good ortholog for thi2, but not so sure it is an assembly factor. SGD summary for THI4 "Thiazole synthase; abundant protein involved in the formation of the thiazole moiety of thiamine during thiamine biosynthesis; acts more as a co-substrate rather than an enzyme by providing the sulphur source for thiazole formation; undergoes a single turnover only; required for mitochondrial genome stability in response to DNA damaging agents.~ DELETED!

ValWood commented 1 week ago

INteresting.

In S. cerevisiae Mss51 is supposedly "translational"
In pombe it is supposedly "post translations" https://www.pombase.org/reference/PMID:22349564 (so maybe it does both but is masked by other factors, or maybe parts of both are outdated)
Ssc1 is also interesting. We have it as mitochondrial (2Fe-2S) cluster assembly chaperone Ssc1, and being part of the PAM complex, Tim23 associated import motor but nothing about a role in respiratory complex assembly

ValWood commented 1 week ago

Parking this here so I don't forget:

pombase / mitochondrion

respiratory complex assembly/ respirasome assembly #3