#11291 NTR: depolarised mitochondrion

[RFoulger]

With the annotation of proteins involved in mitophagy (removal of damaged mitochondria), we’re suggesting the addition of a new component term for use in GO annotation and for mapping to the PD-map (Parkinson’s Disease map: http://pdmap.uni.lu/pd_map/). The depolarised mitochondrion is a naturally occurring state of the organelle, and mitophagy is a normal process whereby damaged mitochondrion are removed safely from the cell.

depolarized mitochondrion ; GO:NEW
is_a: GO:0005739
PMID:25336644
PMID:23885119
GOC:bf, GOC:pad, GOC:rl, GOC:PARL
broad synonym: damaged mitochondrion [GOC:bf]
broad synonym: defective mitochondrion [GOC:bf]
A mitochondrion in which the mitochondrial membrane potential has been lost or reduced. When the membrane potential is lost, protons and some molecules are able to flow across the outer mitochondrial membrane uninhibited.

Is this within the scope of GO?
Thanks.

[David Hill]

Hi Becky,

I have been pondering this for a few days and it just doesn't sit well to start making classes for damaged organelles. It seems like if we take this route we will end up going down the path of damaged DNA, other organelles etc. If you would like, I will bring this up with the other editors, otherwise my vote would be that this is out of the scope of GO.

-D

[RFoulger]

Hi David,

I agree it's a bit of a strange one, and we mulled it over a fair-bit before submitting the ticket. We requested the term because we're struggling to capture the localisation of some proteins (e.g. PINK1) to depolarised mitochondrion, and we thought this would be the simplest way. At the annotation stage, we'd ideally need to bring in some PATO information or similar. Any ideas how we can capture this in our annotations without the term itself?

thanks!

[Paul Denny]

Hi David,

The outcome of the normal BP, GO:0051882 mitochondrial depolarisation, is a modified compartment consisting of a depolarised mitochondrion. So, why can we not define that in GO?

[Paul Denny]

Another thought on this CC term request - mitochondria become depolarised prior to mitophagic clearance in mammalian reticulocytes as part of the normal process of differentiation e.g. PMID: 18454133, PMID:20080761. No exogenous chemicals or other induction needed - just wild-type cells.
Mitochondrial depolarisation may be necessary for mitophagy (at least in red blood cell precursors), because a block on mitophagy caused by knockout of Nix (Q9Z2F7 - (PMID: 18454133)) is relieved if treat reticulocytes with FCCP (FCCP abolishes mito. membrane potential).

[David Hill]

We discussed this at an ontology developer's meeting and decided that it was out of scope for the ontology. Perhaps a phenotype?

[David Osumi-Sutherland]

I think it may be in scope after all: From reading the papers on this ticket: https://sourceforge.net/p/geneontology/ontology-requests/11456/
it seems that clearance of poorly functioning (depolarised) mitochondria occurs all the time. Moreover, elements of the pathway that flags mitochondria for mitophagy are normally cytosolic but localize to depolarized mitochondria (see Parkin). So, I think it makes sense to add this term so that it can be used for annotations of such proteins.

Re precedent: we have 'apoptotic body'

[David Osumi-Sutherland]

Some primary evidence
http://emboj.embopress.org/content/embojnl/27/2/433.full.pdf

[David Osumi-Sutherland]

As a result of discussion in editors SF meeting, we agreed not to add this as we generally do not make CC terms based on some change of quality.

We still need a way for Paul to annotate localization of Parkin to mitochondria when they become depolarised.

Perhaps process + 2 annotation extensions:

'protein localization to mitochondrion' and ('transports or maintains localization of' some Parkin) and ('happens during' some 'mitochondrial depolarization')

Still think it would be much clearer for users if we could do this with direct annotation to CC.