Neurobiology of Disease (Aug 2022)
Neuron-astrocyte transmitophagy is altered in Alzheimer's disease
- Riikka Lampinen,
- Irina Belaya,
- Liudmila Saveleva,
- Jeffrey R. Liddell,
- Dzhessi Rait,
- Mikko T. Huuskonen,
- Raisa Giniatullina,
- Annika Sorvari,
- Liisi Soppela,
- Nikita Mikhailov,
- Isabella Boccuni,
- Rashid Giniatullin,
- Marcela Cruz-Haces,
- Julia Konovalova,
- Marja Koskuvi,
- Andrii Domanskyi,
- Riikka H. Hämäläinen,
- Gundars Goldsteins,
- Jari Koistinaho,
- Tarja Malm,
- Sweelin Chew,
- Kirsi Rilla,
- Anthony R. White,
- Nicholas Marsh-Armstrong,
- Katja M. Kanninen
Affiliations
- Riikka Lampinen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Irina Belaya
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Liudmila Saveleva
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Jeffrey R. Liddell
- Department of Pharmacology & Therapeutics, University of Melbourne, Australia
- Dzhessi Rait
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Mikko T. Huuskonen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Raisa Giniatullina
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Annika Sorvari
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Liisi Soppela
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Nikita Mikhailov
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Isabella Boccuni
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Rashid Giniatullin
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Marcela Cruz-Haces
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Julia Konovalova
- Institute of Biotechnology, University of Helsinki, Finland
- Marja Koskuvi
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Andrii Domanskyi
- Institute of Biotechnology, University of Helsinki, Finland
- Riikka H. Hämäläinen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Gundars Goldsteins
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Jari Koistinaho
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Neuroscience Center, University of Helsinki, Finland
- Tarja Malm
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Sweelin Chew
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
- Kirsi Rilla
- Institute of Biomedicine, University of Eastern Finland, Finland
- Anthony R. White
- Mental Health Program, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Australia
- Nicholas Marsh-Armstrong
- Department of Ophthalmology and Vision Science, University of California Davis, USA
- Katja M. Kanninen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Corresponding author at: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70210 Kuopio, Finland.
- Journal volume & issue
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Vol. 170
p. 105753
Abstract
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 of neuronal mitochondria is significantly increased in astrocytes isolated from AD mouse brains. We also demonstrate that the degradation of neuronal mitochondria by astrocytes is increased in AD mice at the age of 6 months onwards. Furthermore, we 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 AD astrocytes together with significant increases in the mitophagy regulator and reactive oxygen species in aged AD astrocytes. These findings demonstrate altered neuron-supporting functions of AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.
