BCH 445, pertinent papers.docx

4 Pages
Unlock Document

University of Toronto St. George
Dr.Mc Quibban

MITOPHAGY 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. Mitophagy again: Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy Parkin - Component of E3 ubiquitin ligase complex that mediates proteasomal degradation of targets PINK1 -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 52 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 DAMAGED MITOCHONDRIA Proposed mechanism à depolarization of mitochondria à stabilization of PINK-1 on mitochondrial membrane à Mfn2 phosphorylation à attraction and binding with Parkin à MITOPHAGY Pexophagy NBR1 acts as an autophagy receptor for peroxisomes Selective macro-autophagy Ubiquitinated substrates recognized by autophagic receptors (e.g. p62, NBR1) and then degraded in lysosomes Pexophagy 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 Pexophagy 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. Mitochondrial disease: • RGCs are neurons that integrate information from photoreceptors and project into the brain • Mitochondrial inner membrane fusion • Regulates mitochondrial network and morphology with
More Less

Related notes for BCH445H1

Log In


Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.