Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases

Niamh M.C. Connolly, Pierre Theurey, Vera Adam-Vizi, Nicolas G. Bazan, Paolo Bernardi, Juan P. Bolaños, Carsten Culmsee, Valina Dawson, Mohanish Deshmukh, Michael R. Duchen, Heiko Düssmann, Gary Fiskum, Maria F. Galindo, Giles E. Hardingham, J Marie Hardwick, Mika B. Jekabsons, Elizabeth A. Jonas, Joaquin Jordán, Stuart A. Lipton, Giovanni Manfredi & 26 others Mark P. Mattson, Beth Ann McLaughlin, Axel Methner, Anne N. Murphy, Michael P. Murphy, David G. Nicholls, Brian M. Polster, Tullio Pozzan, Rosario Rizzuto, Jorgina Satrústegui, Ruth S. Slack, Raymond A. Swanson, Russell H. Swerdlow, Yvonne Will, Zheng Ying, Alvin Joselin, Anna Gioran, Catarina Moreira Pinho, Orla Watters, Manuela Salvucci, Irene Llorente-Folch, David S. Park, Daniele Bano, Maria Ankarcrona, Paola Pizzo, Jochen H.M. Prehn

Research output: Contribution to journalArticle

Abstract

Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium (www.cebiond.org), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.

Original languageEnglish (US)
Pages (from-to)542-572
Number of pages31
JournalCell Death and Differentiation
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Neurodegenerative Diseases
Guidelines
Energy Metabolism
Time-Lapse Imaging
Neurons
Nerve Degeneration
Mitochondrial Membrane Potential
Optical Imaging
Huntington Disease
Oxygen Consumption
NAD
Parkinson Disease
Consensus
Alzheimer Disease
Theoretical Models
Pathology
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Connolly, N. M. C., Theurey, P., Adam-Vizi, V., Bazan, N. G., Bernardi, P., Bolaños, J. P., ... Prehn, J. H. M. (2018). Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases. Cell Death and Differentiation, 25(3), 542-572. https://doi.org/10.1038/s41418-017-0020-4

Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases. / Connolly, Niamh M.C.; Theurey, Pierre; Adam-Vizi, Vera; Bazan, Nicolas G.; Bernardi, Paolo; Bolaños, Juan P.; Culmsee, Carsten; Dawson, Valina; Deshmukh, Mohanish; Duchen, Michael R.; Düssmann, Heiko; Fiskum, Gary; Galindo, Maria F.; Hardingham, Giles E.; Hardwick, J Marie; Jekabsons, Mika B.; Jonas, Elizabeth A.; Jordán, Joaquin; Lipton, Stuart A.; Manfredi, Giovanni; Mattson, Mark P.; McLaughlin, Beth Ann; Methner, Axel; Murphy, Anne N.; Murphy, Michael P.; Nicholls, David G.; Polster, Brian M.; Pozzan, Tullio; Rizzuto, Rosario; Satrústegui, Jorgina; Slack, Ruth S.; Swanson, Raymond A.; Swerdlow, Russell H.; Will, Yvonne; Ying, Zheng; Joselin, Alvin; Gioran, Anna; Moreira Pinho, Catarina; Watters, Orla; Salvucci, Manuela; Llorente-Folch, Irene; Park, David S.; Bano, Daniele; Ankarcrona, Maria; Pizzo, Paola; Prehn, Jochen H.M.

In: Cell Death and Differentiation, Vol. 25, No. 3, 01.03.2018, p. 542-572.

Research output: Contribution to journalArticle

Connolly, NMC, Theurey, P, Adam-Vizi, V, Bazan, NG, Bernardi, P, Bolaños, JP, Culmsee, C, Dawson, V, Deshmukh, M, Duchen, MR, Düssmann, H, Fiskum, G, Galindo, MF, Hardingham, GE, Hardwick, JM, Jekabsons, MB, Jonas, EA, Jordán, J, Lipton, SA, Manfredi, G, Mattson, MP, McLaughlin, BA, Methner, A, Murphy, AN, Murphy, MP, Nicholls, DG, Polster, BM, Pozzan, T, Rizzuto, R, Satrústegui, J, Slack, RS, Swanson, RA, Swerdlow, RH, Will, Y, Ying, Z, Joselin, A, Gioran, A, Moreira Pinho, C, Watters, O, Salvucci, M, Llorente-Folch, I, Park, DS, Bano, D, Ankarcrona, M, Pizzo, P & Prehn, JHM 2018, 'Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases', Cell Death and Differentiation, vol. 25, no. 3, pp. 542-572. https://doi.org/10.1038/s41418-017-0020-4
Connolly, Niamh M.C. ; Theurey, Pierre ; Adam-Vizi, Vera ; Bazan, Nicolas G. ; Bernardi, Paolo ; Bolaños, Juan P. ; Culmsee, Carsten ; Dawson, Valina ; Deshmukh, Mohanish ; Duchen, Michael R. ; Düssmann, Heiko ; Fiskum, Gary ; Galindo, Maria F. ; Hardingham, Giles E. ; Hardwick, J Marie ; Jekabsons, Mika B. ; Jonas, Elizabeth A. ; Jordán, Joaquin ; Lipton, Stuart A. ; Manfredi, Giovanni ; Mattson, Mark P. ; McLaughlin, Beth Ann ; Methner, Axel ; Murphy, Anne N. ; Murphy, Michael P. ; Nicholls, David G. ; Polster, Brian M. ; Pozzan, Tullio ; Rizzuto, Rosario ; Satrústegui, Jorgina ; Slack, Ruth S. ; Swanson, Raymond A. ; Swerdlow, Russell H. ; Will, Yvonne ; Ying, Zheng ; Joselin, Alvin ; Gioran, Anna ; Moreira Pinho, Catarina ; Watters, Orla ; Salvucci, Manuela ; Llorente-Folch, Irene ; Park, David S. ; Bano, Daniele ; Ankarcrona, Maria ; Pizzo, Paola ; Prehn, Jochen H.M. / Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases. In: Cell Death and Differentiation. 2018 ; Vol. 25, No. 3. pp. 542-572.
@article{5f5bc3a4406340b4b618c91a3d2fe67d,
title = "Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases",
abstract = "Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium (www.cebiond.org), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.",
author = "Connolly, {Niamh M.C.} and Pierre Theurey and Vera Adam-Vizi and Bazan, {Nicolas G.} and Paolo Bernardi and Bola{\~n}os, {Juan P.} and Carsten Culmsee and Valina Dawson and Mohanish Deshmukh and Duchen, {Michael R.} and Heiko D{\"u}ssmann and Gary Fiskum and Galindo, {Maria F.} and Hardingham, {Giles E.} and Hardwick, {J Marie} and Jekabsons, {Mika B.} and Jonas, {Elizabeth A.} and Joaquin Jord{\'a}n and Lipton, {Stuart A.} and Giovanni Manfredi and Mattson, {Mark P.} and McLaughlin, {Beth Ann} and Axel Methner and Murphy, {Anne N.} and Murphy, {Michael P.} and Nicholls, {David G.} and Polster, {Brian M.} and Tullio Pozzan and Rosario Rizzuto and Jorgina Satr{\'u}stegui and Slack, {Ruth S.} and Swanson, {Raymond A.} and Swerdlow, {Russell H.} and Yvonne Will and Zheng Ying and Alvin Joselin and Anna Gioran and {Moreira Pinho}, Catarina and Orla Watters and Manuela Salvucci and Irene Llorente-Folch and Park, {David S.} and Daniele Bano and Maria Ankarcrona and Paola Pizzo and Prehn, {Jochen H.M.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1038/s41418-017-0020-4",
language = "English (US)",
volume = "25",
pages = "542--572",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases

AU - Connolly, Niamh M.C.

AU - Theurey, Pierre

AU - Adam-Vizi, Vera

AU - Bazan, Nicolas G.

AU - Bernardi, Paolo

AU - Bolaños, Juan P.

AU - Culmsee, Carsten

AU - Dawson, Valina

AU - Deshmukh, Mohanish

AU - Duchen, Michael R.

AU - Düssmann, Heiko

AU - Fiskum, Gary

AU - Galindo, Maria F.

AU - Hardingham, Giles E.

AU - Hardwick, J Marie

AU - Jekabsons, Mika B.

AU - Jonas, Elizabeth A.

AU - Jordán, Joaquin

AU - Lipton, Stuart A.

AU - Manfredi, Giovanni

AU - Mattson, Mark P.

AU - McLaughlin, Beth Ann

AU - Methner, Axel

AU - Murphy, Anne N.

AU - Murphy, Michael P.

AU - Nicholls, David G.

AU - Polster, Brian M.

AU - Pozzan, Tullio

AU - Rizzuto, Rosario

AU - Satrústegui, Jorgina

AU - Slack, Ruth S.

AU - Swanson, Raymond A.

AU - Swerdlow, Russell H.

AU - Will, Yvonne

AU - Ying, Zheng

AU - Joselin, Alvin

AU - Gioran, Anna

AU - Moreira Pinho, Catarina

AU - Watters, Orla

AU - Salvucci, Manuela

AU - Llorente-Folch, Irene

AU - Park, David S.

AU - Bano, Daniele

AU - Ankarcrona, Maria

AU - Pizzo, Paola

AU - Prehn, Jochen H.M.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium (www.cebiond.org), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.

AB - Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium (www.cebiond.org), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.

UR - http://www.scopus.com/inward/record.url?scp=85037678087&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037678087&partnerID=8YFLogxK

U2 - 10.1038/s41418-017-0020-4

DO - 10.1038/s41418-017-0020-4

M3 - Article

VL - 25

SP - 542

EP - 572

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 3

ER -