In healthy cells pink 1 makes its way into the inner mitochondrial membrane through the tom 40
tim system via its stop transfer signal. When in the inner mitochondrial membrane it gets
degraded by the rhomboid protease PARL. In mitochondria with a destabilized membrane
potential, PINK1 gets integrated into the outer mitochondrial membrane... Likely through tom40
and sam. In this situation, PARKIN an E3 can ubiquitinate mitochondria and therefore target
them for autophagic degradation.
Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy
Parkin - Component of E3 ubiquitin ligase complex that mediates proteasomal degradation of
-Protects against stress-induced mitochondrial dysfunction
-Recruits Parkin to mitochondria during mitophagy
PINK1 52cumulates at MOM and then translocates to the cytosol
PINK1 binds to Parkin
Middle section of PINK1 kinase domain
R1 domain of Parkin
PINK1 52terferes with Parkin translocation & mitophagy
In the first paper they assume that pink1 and parkin can form a complex that induces
mitophagy... in the next they state that pink1 is able to inhibit parkin induced mitophagy by
dissalowing for parkin import.
PINK-1 PHOSPHORYLATED MITOFUSIN 2 IS A PARKIN RECEPTOR FOR CULLING
Proposed mechanism à depolarization of mitochondria à stabilization of PINK-1 on
mitochondrial membrane à Mfn2 phosphorylation à attraction and binding with Parkin
NBR1 acts as an autophagy receptor for peroxisomes
Ubiquitinated substrates recognized by autophagic receptors (e.g. p62, NBR1) and then
degraded in lysosomes
Selective macro-autophagy of peroxisomes
p62 has already been shown to have a role in selective degradation of Ub-labelled peroxisomes NBR1 is required for pexophagy
Promotes clustering & targeting to lysosomes
Can act independently of p62
But p62 increases efficiency
J and UBA domains required
J domain required for clustering
UBA domain required for targeting specific organelles
PpAtg30 Tags Peroxisomes for Turnover by Selective Autophagy
A. Cell growing in rich medium have few peroxisomes.
B. Induction of peroxisome biogenesis also leads to increased expression of peroxins and
PpAtg30. PpAtg30 localizes at peroxisomal membranes due to Pex3/14.
C. Unknown kinase phosphorylates PpAtg30. PpAtg30 delivers peroxisomes for pexophagy
through interactions with PpAtg11/17.
D. Peroxisomes + Phosphorylated PpAtg30 sequestered by arm and MIPA.
• RGCs are neurons that integrate information from photoreceptors and project into the
• Mitochondrial inner membrane fusion
• Regulates mitochondrial network and morphology with