#11456 new term request - PINK1-PARKIN dependent mitophagy pathway

[Paul Denny]

PINK1-PARKIN dependent mitophagy pathway
Human PINK1 Q9BXM7
Human Parkin O60260
Specifically, in PMID: 24821430 it is stated that:

“…when a dysfunctional mitochondrion cannot be repaired, it is cleared through mitophagy. Under basal conditions, the protein kinase Pink1 is imported into the mitochondrial intermembrane space, where it is cleaved by 2 proteases and subsequently degraded. However, upon mitigation of the MMP (mitochondrial membrane potential), Pink1 is no longer cleaved. The protein then phosphorylates and activates the E3 ubiquitin ligase Parkin. Parkin, along with E2 ligases such as Rad6, initiates mitophagy by ubiquitinating target proteins.”

The details of the pathway remain hazy, but I think there is plenty of evidence in the literature (e.g. PMID: 20736035, PMID: 23985961) that there is a distinct PINK1-PARKIN dependent mitophagy pathway.
Genetic evidence from Drosophila place PINK1 and Parkin in a common pathway (PMID: 24149988), with PINK1 upstream of parkin. Many papers talk about "Parkin initiates mitophagy" (PMID: 24149988).

Possible definition:
The Pink1-Parkin dependent mitophagy pathway initiates the autophagic process in which mitochondria are delivered to the vacuole and degraded in response to changing cellular conditions.

[Paul Denny]

[Paul Denny]

Hi David
This may need a separate SF ticket, but I think there is also a need for another term - possibly child to the one I’ve requested - called "Parkin-mediated mitophagy” see e.g.

PMID: 25336644
PMID: 25294927
PMID: 24896179

[David Osumi-Sutherland]

How's this. Perhaps too much detail?

[Term]
id: GO:0098787
name: PINK1-PARKIN dependent mitophagy pathway
namespace: biological_process
def: "A pathway involving PINK1 and PARKIN, that initiates mitophagy in damaged or malfunctioning mitochondria. In mitochondria with normal membrane potential, PINK1 is imported and degraded. This process is impaired in mitochondria with reduced membrane potential allowing PINK1 to recruit and phosphorylate PARKIN. PARKIN is then imported into mitochondria where it ubiquitinates target proteins, initiaing mitophagy." [GOC:dos, GOC:pd, PMID:24149988]
comment: An example of this pathway is found in humans where PINK1 corrsponds to Uniprot:Q9BXM7 and Parkin to Uniprot:O60260
is_a: GO:0050789 ! regulation of biological process
relationship: regulates GO:0000422 ! mitochondrion degradation

[Valerie Wood]

I would not request a new GO term for "gene X dependent process Y"
UNLESS it is clearly known that there are independent processes which are generally labelled in this way by the community.

Otherwise you will end up with a separate GO term for every gene required in a pathway.
Just annotate to the pathway?

If parkin is required for mitophagy how does

PINK1-PARKIN dependent mitophagy pathway
or
Parkin-mediated mitophagy
differ from
"mitophagy"

Val
?

[David Osumi-Sutherland]

Scratch that. I've decided to add a more general class instead:

activation of mitophagy in response to mitochondrial depolarization
EquivalentTo: 'response to mitochondrial deploarization'* that positively_regulates some 'mitochondrial degredation'

*TBA - see https://sourceforge.net/p/geneontology/ontology-requests/11348/

[David Osumi-Sutherland]

Hi Val, Just noticed your comment. Had independently come to a similar conclusion. "GO:0098787; PINK1-PARKIN dependent mitophagy pathway" not committed to go svn yet, so I will just delete and go with the more general term.

[Valerie Wood]

God, i'm the GO police aren't I? Sorry!

[David Osumi-Sutherland]

Someone's got to keep us on the straight and narrow. :P