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mitochondrial DNA & ER inheritance #18417

Closed ValWood closed 3 years ago

ValWood commented 4 years ago

GO:0033955
mitochondrial DNA inheritance Definition The process in which copies of the mitochondrial genome are distributed into daughter mitochondria upon mitochondrial fission.

13 annotation 1 PomBase 1 TAIR 1 MGI 10 GeneDB T. brucie

As far as I can tell, this is a phenotype, not an active process. DNA are partitioned arbitrarily when mitochondria undergo fission (but most daughters get some copied because there are 1000's) I am removing the PomBase annotation. Should the term be obsoleted? Or merged into the (current) sibling "mitochondrial fission" as a related synonym?

ValWood commented 4 years ago

Also the child term

GO:0033955 JSON mitochondrial DNA inheritance Biological Process

Definition (GO:0033955 GONUTS page) The process in which copies of the mitochondrial genome are distributed into daughter mitochondria upon mitochondrial fission.

No annotations, process does not exist?

ukemi commented 4 years ago

Are you sure? PMID:25237825

ukemi commented 4 years ago

PMID:29880721

pgaudet commented 4 years ago

@ValWood You mention GO:0033955 twice - I dont see a child for GO:0033955; can you check ?

pgaudet commented 4 years ago

Looking at the review PMID:24183694, it sound like mitochondrial DNA inheritance corresponds to mt DNA replication + segregation.

I agree many of the annotations just look like phenotypes. I think the pombase annotation corresponds to 'GO:0090146 establishment of mitochondrion localization involved in mitochondrial fission' - what do you think ?

I propose we review the annotations before deciding what to do here.

ValWood commented 4 years ago

I mean also:

GO:0000002 mitochondrial genome maintenance Definition The maintenance of the structure and integrity of the mitochondrial genome; includes replication and segregation of the mitochondrial chromosome.

However , this has lots of annotations.

I have been under the impression for many years that these are phenotypes. I have never seen an active mechanism for "mitochondrial DNA inheritance" as defined here.

Fission happens and large DNA copy number means that most daughter mitochondria will have plenty.

This makes GO:0000002 mitochondrial genome maintenance unnecessary

I will have a quick look at the papers David suggested.

ValWood commented 4 years ago

i.e there is no mitochondrial segregation machinery

Its replication + mitochondrial fission

But it wouldn't make sense as a parent, it's just an "observation"

ukemi commented 4 years ago

The idea of the mitochondrial bottleneck during oogenesis was what I had in mind, but it looks like the modern thought on this is that it is just probability and there might not be a genetic mechanism. Still worth investigating further.

ValWood commented 4 years ago

Isn't that about

GO:0000001 mitochondrion inheritance Definition The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. PMID:10873824 PMID:11389764

This is OK (although the mechanism appears to also be dependent on fission) Fission increases during division so there are more small mitochondria increasing the chance of each daughter having mitochondria:

PMID:30602572 Additionally, increased mitochondrial fragmentation upon the onset of mitosis has also been observed (3), perhaps indicating a binomial partitioning or independent segregation mechanism for mitochondrial dis- tribution wherein each mitochondrion in the mother has a 50% likelihood of being partitioned into either of the daughter cells by virtue of symmetric division and without the involvement of active processes. Although the molecular players that effect fission and fusion have been identified in several systems, the cellular signals that regulate these events are largely elusive. Here, we demonstrate that mitochondria piggyback on dynamic microtubules to selectively undergo fission when microtu- bules depolymerize. Reorganization of interphase microtu- bules into the nucleus when cells prepare for division also provide the cue for increased mitochondrial fission. We quantified the number of mitochondria in mother cells immediately after formation of mitotic spindle within the nucleus and the number of mitochondria in the resulting daughter cells and confirmed that the partitioning was indeed a good fit to a binomial distribution, indicating that an independent segregation mechanism serves to distribute mito- chondria into the two daughter cells. We determined that the presence of long and stabilized microtubules was inhibitory to unopposed fission even when Dnm1 was overexpressed. Finally, we discovered that microtubule-bound mitochondria were unlikely to undergo fission due to the unavailability of space between microtubules and mitochondria for the forma- tion of the Dnm1 ring.

ValWood commented 4 years ago

Its pretty cool. Fission is inhibited by association with interphase microtubules.

This actually makes it difficult to separate ""fission" from "inheritance" but I was going to ignore this for now. It is more meaningful than the

"DNA inheritance" and "maintenance terms".

(I removed the PomBase annotation yesterday)

ValWood commented 4 years ago

The annotations seem to be phenotypes;

TIM17 Essential component of the TIM23 complex   mitochondrial genome maintenance   SGD Saccharomyces cerevisiae S288C IGI SGD:S000004347 mitochondrial import inner membrane translocase subunit tim-17 pthr10485 protein   PMID:18826960 20120501
  TIM17 Essential component of the TIM23 complex   mitochondrial genome maintenance   SGD Saccharomyces cerevisiae S288C IGI SGD:S000004676 mitochondrial import inner membrane translocase subunit tim-17 pthr10485 protein   PMID:18826960 20120501
  MDV1 Peripheral protein of cytosolic face of mitochondrial outer membrane   mitochondrial genome maintenance   SGD Saccharomyces cerevisiae S288C IMP   family not named pthr19857 protein   PMID:11038182 20010118
  MEF2 Mitochondrial elongation factor involved in translational elongation   mitochondrial genome maintenance   SGD Saccharomyces cerevisiae S288C IMP   family not named pthr43261 protein   PMID:21414316 20140325

Protein of unknown function mitochondrial genome maintenance SGD Saccharomyces cerevisiae S288C IMP protein PMID:19751518 20091009 REX2 3'-5' RNA exonuclease mitochondrial genome maintenance SGD Saccharomyces cerevisiae S288C IMP oligoribonuclease, mitochondrial pthr11046 protein PMID:9933355 20080611 REX2 3'-5' RNA exonuclease mitochondrial genome maintenance SGD Saccharomyces cerevisiae S288C IGI SGD:S000004917 oligoribonuclease, mitochondrial pthr11046 protein PMID:9933355 20080611 REX2 3'-5' RNA exonuclease mitochondrial genome maintenance SGD Saccharomyces cerevisiae S288C IGI SGD:S000006228 oligoribonuclease, mitochondrial pthr11046 protein PMID:9933355 20080611

etc etc

ValWood commented 4 years ago

The same seems to apply to ER inheritance https://www.ebi.ac.uk/QuickGO/annotations?goUsage=descendants&goUsageRelationships=is_a,part_of,occurs_in&goId=GO:0048309&evidenceCode=ECO:0000269&evidenceCodeUsage=descendants

21 EXP all IMP from SGD

I don't think there is any active partitioning mechanism. Will check later with authors of curation I am checking.

ValWood commented 4 years ago

I checked with 2 pombe researchers who study ER organization:

1 my feeling is that there is no active 'partitioning mechanism' - beyond attaching the ER to the cortex as cells grow. pombe divides in the middle so that takes care of ER distribution to both daughter cells.

2 I agree with Snezhka. I also do not imagine an active mechanism just for ER inheritance – I feel that 1) ER-PM contacts 2) connection with nuclear envelope 3) actomyosin transport (towards tips) all can take care of ER dispersal to daughter cells.

So, unless there is any active mechanism in budding yeast, because of budding, these seem like a phenotype of abnormal ER organization @srengel could you check that?

srengel commented 4 years ago

@ValWood is the suggestion to move the ER inheritance ones up to ER organization?

i can move the mito genome maintenance ones to be phenotype annotations instead of GO.

ValWood commented 4 years ago

I hadn't thought about the ER one. Yes merge up and make related synonym would work?

ValWood commented 4 years ago

I wasn't sure if budding yeast had some 'special' mechanism because of budding, but when I looked most of the annotations were just to the reticulon-and other general ER membrane organization things. v

ValWood commented 4 years ago

Although there is not identified mechanism fpr mitochondrial inheritance in mitotic/somatic cells There is now a new paper describing a mechanism for inheritance in mitochondria during meiosis in isogamous organisms, by 'tethering'

PMID:31582398 Title | Cortical tethering of mitochondria by the anchor protein Mcp5 enables uniparental inheritance.

ValWood commented 4 years ago

there are several strategies for uniparental inheritance in meiosis

including subjecting paternal mitochondria to (1) sequestration and ex- clusion (Yu and Russell, 1992), (2) selective lysosomal degrada- tion via ubiquitination (Sutovsky et al., 1999, 2000), or (3) simple dilution due to the large size of the female gamete in comparison to the male gamete (Birky, 1995; Wilson and Xu, 2012). (this one sounds passive)

So, there probab ly should. be a term for "mitochondrial inheritance during meiosis"

ValWood commented 4 years ago

~Also active process in S. cerevisiae to get mitochondria into the bud (vegetative growth) Tethering of mitochondria by Num1 aids in the retention of a mitochondrial population within the mother cell (Lackner et al., 2013), while another population is transported on actin cables to the bud by the activity of the myosin V, Myo2 (Altmann et al., 2008; Fo ̈rtsch et al., 2011).

ValWood commented 4 years ago

See also https://github.com/geneontology/go-ontology/issues/12828

need to look at GO:0051646 mitochondrion localization GO:0048311 mitochondrion distribution GO:0051659 maintenance of mitochondrion location GO:0051654 establishment of mitochondrion localization GO:0048312 intracellular distribution of mitochondria (syn mitochondrion positioning within cell) GO:0000001 mitochondrion inheritance GO:0033955 mitochondrial DNA inheritance GO:0000266. mitochondrial fission

ValWood commented 4 years ago
Screenshot 2020-03-29 at 15 36 02
ValWood commented 4 years ago

We should review to see what processes are annotated

All I have figured so far

Fission yeast In pombe there is no mechanism for "segregation of mitochondria In interphase there are more larger mitochondria. During mitosis there is a lot of mitochondrial fission to give larger numbers of smaller mitochondria. https://www.pombase.org/reference/PMID:30602572 as a consequence, most cells will get some mitochondria in any division

Mitochondria are critically tethered in meiosis and this enables uniparental inheritance https://www.pombase.org/reference/PMID:31582398

I annotated these to an adaptor term and "mitochondrion localization" I could have used any of the other terms.

ValWood commented 3 years ago

Suggestions

Is a process. It just happens during fission, there is no separate mechanism for segregation

-> action, merge into parent GO:0000266 JSON

This term seems unnecessary, merge into 'mitochondrion fission' parent or obsolete? (no annotations) Also, it is defined as directed movement which would be wrong (directed movement is transport) so obsoletion might be better?

I don't know what this means ? It has no annotations. Is the nucleoid involved in fission - I have never read about this, is there a reference? (I apologise if I ever requested this term!)

I'm confused by this term. I think the 'between and within cells' part is so that it covers localization. within a cell, AND inheritance. In this case, it can merge into GO:0051646 mitochondrion localization because "mitochondrion inheritance" is already a descendant, this term is redundant.

has 22 EXP annotations. Some annotation seem to be describing 'fission' and in these cases localization is just a consequence (phenotype)

but I don't know enough about how mitochondria move around in animal cells. Some of these annotations might be better described as transport as they possibly involve the. cytoskeleton, I'm not sure.....

pgaudet commented 3 years ago

Taxon constraint for ER inheritance: https://github.com/geneontology/go-ontology/compare/master...pgaudet-patch-29?quick_pull=1

pgaudet commented 3 years ago

@ValWood How about this:

pgaudet commented 3 years ago

Dear all,

The proposal has been made to obsolete GO:0090146 establishment of mitochondrion localization involved in mitochondrial fission GO:0090147 regulation of establishment of mitochondrion localization involved in mitochondrial fission GO:0090145 mitochondrial nucleoid organization involved in mitochondrial fission No annotations

GO:0033955 mitochondrial DNA inheritance - 12 EXP, annotation review ticket https://github.com/geneontology/go-annotation/issues/3674

The reason for obsoletion is that those terms represent phenotypes/observations of other processes, such as consider GO:0000002 mitochondrial genome maintenance and GO:0000266 mitochondrial fission.

There are no mappings, those terms are not present in any subsets.

We are opening a comment period for this proposed obsoletion. We’d like to proceed and obsolete this term on March 17th. Unless objections are received by March 17th, 2021, we will assume that you agree to this change.

You can comment on the ticket here: https://github.com/geneontology/go-ontology/issues/18417

Thanks, Pascale