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

doi:10.1016/j.nbd.2022.105753

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 MalmSweelin Chew, Kirsi Rilla, Anthony R. White, Nicholas Marsh-Armstrong, Katja M Kanninen

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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.

Original language	English
Article number	105753
Journal	Neurobiology of Disease
DOIs	https://doi.org/10.1016/j.nbd.2022.105753
Publication status	Published - May 2022
Externally published	Yes
MoE publication type	A1 Journal article-refereed

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Lampinen, R., Belaya, I., Saveleva, L., Liddell, J. R., Rait, D., Huuskonen, M. T., Giniatullina, R., Sorvari, A., Soppela, L., Mikhailov, N., Boccuni, I., Giniatullin, R., Cruz-Haces, M., Konovalova, J., Koskuvi, M., Domanskyi, A., Hämäläinen, R. H., Goldsteins, G., Koistinaho, J., ... Kanninen, K. M. (2022). Neuron-astrocyte transmitophagy is altered in Alzheimer's disease. Neurobiology of Disease, Article 105753. https://doi.org/10.1016/j.nbd.2022.105753

@article{6dc84a86ed3d4b349be793be1d5feb00,

title = "Neuron-astrocyte transmitophagy is altered in Alzheimer's disease",

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.",

author = "Riikka Lampinen and Irina Belaya and Liudmila Saveleva and Liddell, \{Jeffrey R.\} and Dzhessi Rait and Huuskonen, \{Mikko T.\} and Raisa Giniatullina and Annika Sorvari and Liisi Soppela and Nikita Mikhailov and Isabella Boccuni and Rashid Giniatullin and Marcela Cruz-Haces and Julia Konovalova and Marja Koskuvi and Andrii Domanskyi and H{\"a}m{\"a}l{\"a}inen, \{Riikka H.\} and Gundars Goldsteins and Jari Koistinaho and Tarja Malm and Sweelin Chew and Kirsi Rilla and White, \{Anthony R.\} and Nicholas Marsh-Armstrong and Kanninen, \{Katja M\}",

year = "2022",

month = may,

doi = "10.1016/j.nbd.2022.105753",

language = "English",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Elsevier",

}

Lampinen, R, Belaya, I, Saveleva, L, Liddell, JR, Rait, D, Huuskonen, MT, Giniatullina, R, Sorvari, A, Soppela, L, Mikhailov, N, Boccuni, I, Giniatullin, R, Cruz-Haces, M, Konovalova, J, Koskuvi, M, Domanskyi, A, Hämäläinen, RH, Goldsteins, G, Koistinaho, J, Malm, T, Chew, S, Rilla, K, White, AR, Marsh-Armstrong, N & Kanninen, KM 2022, 'Neuron-astrocyte transmitophagy is altered in Alzheimer's disease', Neurobiology of Disease. https://doi.org/10.1016/j.nbd.2022.105753

TY - JOUR

T1 - Neuron-astrocyte transmitophagy is altered in Alzheimer's disease

AU - Lampinen, Riikka

AU - Belaya, Irina

AU - Saveleva, Liudmila

AU - Liddell, Jeffrey R.

AU - Rait, Dzhessi

AU - Huuskonen, Mikko T.

AU - Giniatullina, Raisa

AU - Sorvari, Annika

AU - Soppela, Liisi

AU - Mikhailov, Nikita

AU - Boccuni, Isabella

AU - Giniatullin, Rashid

AU - Cruz-Haces, Marcela

AU - Konovalova, Julia

AU - Koskuvi, Marja

AU - Domanskyi, Andrii

AU - Hämäläinen, Riikka H.

AU - Goldsteins, Gundars

AU - Koistinaho, Jari

AU - Malm, Tarja

AU - Chew, Sweelin

AU - Rilla, Kirsi

AU - White, Anthony R.

AU - Marsh-Armstrong, Nicholas

AU - Kanninen, Katja M

PY - 2022/5

Y1 - 2022/5

N2 - 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.

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 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.

UR - http://dx.doi.org/10.1016/j.nbd.2022.105753

U2 - 10.1016/j.nbd.2022.105753

DO - 10.1016/j.nbd.2022.105753

M3 - Article

SN - 0969-9961

JO - Neurobiology of Disease

JF - Neurobiology of Disease

M1 - 105753

ER -

Neuron-astrocyte transmitophagy is altered in Alzheimer's disease

Abstract

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