Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease

Liang Zhang, Sergey Trushin, Trace A. Christensen, Benjamin V. Bachmeier, Benjamin Gateno, Andreas Schroeder, Jia Yao, Kie Itoh, Hiromi Sesaki, Wayne W. Poon, Karen H. Gylys, Emily R. Patterson, Joseph E Parisi, Roberta Diaz Brinton, Jeffrey L Salisbury, Eugenia D Trushina

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.

Original languageEnglish (US)
Article number18725
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 5 2016

Fingerprint

Mitochondrial Dynamics
Alzheimer Disease
Mitochondria
Brain
Organelles
Energy Metabolism
Electron Microscopy
Mitochondrial Degradation
Dynamins
Phenotype
GTP Phosphohydrolases
Proteins

ASJC Scopus subject areas

  • General

Cite this

Zhang, L., Trushin, S., Christensen, T. A., Bachmeier, B. V., Gateno, B., Schroeder, A., ... Trushina, E. D. (2016). Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. Scientific Reports, 6, [18725]. https://doi.org/10.1038/srep18725

Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. / Zhang, Liang; Trushin, Sergey; Christensen, Trace A.; Bachmeier, Benjamin V.; Gateno, Benjamin; Schroeder, Andreas; Yao, Jia; Itoh, Kie; Sesaki, Hiromi; Poon, Wayne W.; Gylys, Karen H.; Patterson, Emily R.; Parisi, Joseph E; Diaz Brinton, Roberta; Salisbury, Jeffrey L; Trushina, Eugenia D.

In: Scientific Reports, Vol. 6, 18725, 05.01.2016.

Research output: Contribution to journalArticle

Zhang, L, Trushin, S, Christensen, TA, Bachmeier, BV, Gateno, B, Schroeder, A, Yao, J, Itoh, K, Sesaki, H, Poon, WW, Gylys, KH, Patterson, ER, Parisi, JE, Diaz Brinton, R, Salisbury, JL & Trushina, ED 2016, 'Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease', Scientific Reports, vol. 6, 18725. https://doi.org/10.1038/srep18725
Zhang L, Trushin S, Christensen TA, Bachmeier BV, Gateno B, Schroeder A et al. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. Scientific Reports. 2016 Jan 5;6. 18725. https://doi.org/10.1038/srep18725
Zhang, Liang ; Trushin, Sergey ; Christensen, Trace A. ; Bachmeier, Benjamin V. ; Gateno, Benjamin ; Schroeder, Andreas ; Yao, Jia ; Itoh, Kie ; Sesaki, Hiromi ; Poon, Wayne W. ; Gylys, Karen H. ; Patterson, Emily R. ; Parisi, Joseph E ; Diaz Brinton, Roberta ; Salisbury, Jeffrey L ; Trushina, Eugenia D. / Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. In: Scientific Reports. 2016 ; Vol. 6.
@article{171ddac3abd54521913fc9a6f6fb112b,
title = "Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease",
abstract = "Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, {"}mitochondria-on-a-string{"} (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.",
author = "Liang Zhang and Sergey Trushin and Christensen, {Trace A.} and Bachmeier, {Benjamin V.} and Benjamin Gateno and Andreas Schroeder and Jia Yao and Kie Itoh and Hiromi Sesaki and Poon, {Wayne W.} and Gylys, {Karen H.} and Patterson, {Emily R.} and Parisi, {Joseph E} and {Diaz Brinton}, Roberta and Salisbury, {Jeffrey L} and Trushina, {Eugenia D}",
year = "2016",
month = "1",
day = "5",
doi = "10.1038/srep18725",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease

AU - Zhang, Liang

AU - Trushin, Sergey

AU - Christensen, Trace A.

AU - Bachmeier, Benjamin V.

AU - Gateno, Benjamin

AU - Schroeder, Andreas

AU - Yao, Jia

AU - Itoh, Kie

AU - Sesaki, Hiromi

AU - Poon, Wayne W.

AU - Gylys, Karen H.

AU - Patterson, Emily R.

AU - Parisi, Joseph E

AU - Diaz Brinton, Roberta

AU - Salisbury, Jeffrey L

AU - Trushina, Eugenia D

PY - 2016/1/5

Y1 - 2016/1/5

N2 - Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.

AB - Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.

UR - http://www.scopus.com/inward/record.url?scp=84953303557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953303557&partnerID=8YFLogxK

U2 - 10.1038/srep18725

DO - 10.1038/srep18725

M3 - Article

C2 - 26729583

AN - SCOPUS:84953303557

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 18725

ER -