Journal
AUTOPHAGY
Volume 16, Issue 10, Pages 1925-1927Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2020.1810919
Keywords
Alzheimer; mitophagosome; Nix; PRKN; retrograde transport; RHEB; SNAPIN; synaptic degeneration; synaptic mitochondrial deficits; synaptic mitophagy
Categories
Funding
- National Institutes of Health [R01NS089737, R21NS102780, R01GM135326]
Ask authors/readers for more resources
Mitochondria sustain various essential functions at synaptic terminals. Synaptic mitochondria deficits have been implicated in early Alzheimer disease (AD) pathophysiology. Mitophagy, a selective autophagy for removal of damaged mitochondria, plays a key role in mitochondrial quality control in neurons. However, fundamental questions remain unanswered as to whether mitophagy regulates synaptic mitochondrial integrity and whether AD-associated early deficits in synaptic mitochondria are attributed to mitophagy failure. We have recently revealed that the integrity of synaptic mitochondria is maintained by a coordination of RHEB-mediated mitophagy with dynein- and SNAPIN-driven retrograde transport. We demonstrate that increased mitophagy initiation, coupled with defective retrograde transport, triggers mitophagy stress at AD synapses. Excitingly, SNAPIN-enhanced retrograde transport reduces synaptic mitophagy stress and ameliorates mitochondrial deficits, thereby counteracting synaptic damage in AD mouse brains. Therefore, our study provides new mechanistic insights into how mitophagy facilitates synaptic mitochondrial maintenance and how mitophagy failure exacerbates AD-linked mitochondrial defects and synaptic degeneration. Abbreviation: AD: Alzheimer disease; A beta: amyloid-beta; APP: amyloid beta precursor protein; CCCP: carbonyl cyanidem-chlorophenylhydrazone; LE: late endosome; Delta psi(m), mitochondrial membrane potential; RHEB: Ras homolog enriched in brain; RNAi: RNA interference; shRNA: small hairpin RNA; Tg: transgenic
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available