RT Journal Article
SR Electronic
T1 Alzheimer’s disease alters astrocytic functions related to neuronal support and transcellular internalization of mitochondria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.15.460570
DO 10.1101/2021.09.15.460570
A1 Riikka Lampinen
A1 Irina Belaya
A1 Liudmila Saveleva
A1 Jeffrey R Liddell
A1 Dzhessi Rait
A1 Mikko T Huuskonen
A1 Raisa Giniatullina
A1 Annika Sorvari
A1 Liisi Soppela
A1 Nikita Mikhailov
A1 Isabella Boccuni
A1 Rashid Giniatullin
A1 Marcela Cruz-Haces
A1 Julia Konovalova
A1 Marja Koskuvi
A1 Tuomas Rauramaa
A1 Andrii Domanskyi
A1 Riikka H Hämäläinen
A1 Gundars Goldsteins
A1 Jari Koistinaho
A1 Tarja Malm
A1 Sweelin Chew
A1 Kirsi Rilla
A1 Anthony R White
A1 Nicholas Marsh-Armstrong
A1 Katja M Kanninen
YR 2021
UL http://biorxiv.org/content/early/2021/09/17/2021.09.15.460570.abstract
AB Under physiological conditions in vivo astrocytes internalize and degrade neuronal mitochondria in a process called transmitophagy. Mitophagy is widely reported to be impaired in neurodegeneration but it is unknown whether and how transmitophagy is altered in Alzheimer’s disease (AD). Here we report that the internalization and degradation of neuronal mitochondria are significantly increased in astrocytes isolated from aged AD mouse brains. We also demonstrate for the first time a similar phenomenon between human neurons and AD astrocytes, and in murine hippocampi in vivo. The results suggest the involvement of S100a4 in impaired mitochondrial transfer between neurons and aged AD astrocytes. Significant increases in the mitophagy regulator Ambra1 were observed in the aged AD astrocytes. These findings demonstrate altered neuron-supporting functions of aged AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.Competing Interest StatementThe authors have declared no competing interest.