Catalog

ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.

Article

Mechanism of human PINK1 activation at the TOM complex in a reconstituted system

Preprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.

Article

Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1

Published: Loss-of-function mutations in Parkin cause disruption of mitophagy and are associated with PD. Yet, much of the biology surrounding Parkin function has taken place in artificial cell systems. The authors used human neurons to identify and validate 22 protein targets of Parkin, providing a functional Parkin landscape in neuronal cells.

Protocol

Live cell imaging of yeast cells expressing human PINK1-GFP and the TOM complex subunits

A protocol for live-cell imaging of yeast cells expressing human PINK1 with GFP tag at the C-terminus as well as all the human TOM complex subunits (TOMs 5, 6, 7, 20, 22, 40 and 70).

Article

In situ structural analysis reveals membrane shape transitions during autophagosome formation

Preprint: A hallmark of PD is the failure of quality control mechanisms in the cell, such as autophagy. The authors combined cell biology with correlative cryo-electron tomography in yeast cells to show a high resolution stepwise structural progression of autophagosome biogenesis. Further, they revealed the organelle interactome for growing autophagosomes.

Article

Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1

Published: Mutations in PINK1 and Parkin are implicated in PD via abherrant mitophagy. The authors identified ubiquitylated substrates of endogenous Parkin in mouse neurons by proteomic analysis. They identified and validated 22 protein targets of Parkin that are conserved in human neurons providing a functional Parkin landscape in neuronal cells. View original preprint.

Lab Resource

H9 ES AAVS1-NGN2 FAM134B-/-; PiggyBac-Keima-REEP5

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134B and expressing the indicated Keima-REEP5 ER-phagy flux reporter.

Lab Resource

H9 ES AAVS1-NGN2 CCPG1-/-; PiggyBac-Keima-RAMP4

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor CCPG1 and expressing the indicated Keima-RAMP4 ER-phagy flux reporter.

Lab Resource

H9 ES AAVS1-NGN2 CCPG1-/-; PiggyBac-Keima-REEP5

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor CCPG1 and expressing the indicated Keima-REEP5 ER-phagy flux reporter.

Lab Resource

H9 ES AAVS1-NGN2 FAM134A-/-

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134A.

Lab Resource

H9 ES AAVS1-NGN2 FAM134A-/-; PiggyBac-Keima-RAMP4

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134A and expressing the indicated Keima-RAMP4 ER-phagy flux reporter.

Lab Resource

H9 ES AAVS1-NGN2 FAM134A-/-; PiggyBac-Keima-REEP5

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134A and expressing the indicated Keima-REEP5 ER-phagy flux reporter.

Lab Resource

H9 ES AAVS1-NGN2 FAM134B-/-

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134B.

Lab Resource

H9 ES AAVS1-NGN2 FAM134B-/-; PiggyBac-Keima-RAMP4

Cell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134B and expressing the indicated Keima-RAMP4 ER-phagy flux reporter.