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

被引：128

作者：

Connolly, Niamh M. C. ^{[1
]}

Theurey, Pierre ^{[2
]}

Adam-Vizi, Vera ^{[3
]}

Bazan, Nicolas G. ^{[4
]}

Bernardi, Paolo ^{[2
,5
]}

Bolanos, Juan P. ^{[6
]}

Culmsee, Carsten ^{[7
]}

Dawson, Valina L. ^{[8
,9
,10
,11
,12
]}

Deshmukh, Mohanish ^{[13
]}

Duchen, Michael R. ^{[14
,15
]}

Dussmann, Heiko ^{[1
]}

Fiskum, Gary ^{[16
,17
,18
]}

Galindo, Maria F. ^{[19
]}

Hardingham, Giles E. ^{[20
]}

Hardwick, J. Marie ^{[21
]}

Jekabsons, Mika B. ^{[22
]}

Jonas, Elizabeth A. ^{[23
]}

Jordan, Joaquin ^{[24
]}

Lipton, Stuart A. ^{[25
,26
,27
,28
,29
]}

Manfredi, Giovanni ^{[30
]}

Mattson, Mark P. ^{[31
]}

McLaughlin, BethAnn ^{[32
]}

Methner, Axel ^{[33
]}

Murphy, Anne N. ^{[34
]}

Murphy, Michael P. ^{[35
]}

Nicholls, David G. ^{[36
]}

Polster, Brian M. ^{[14
,16
,17
,18
]}

Pozzan, Tullio ^{[2
,5
]}

Rizzuto, Rosario ^{[2
,5
]}

Satrustegui, Jorgina ^{[37
]}

Slack, Ruth S. ^{[38
]}

Swanson, Raymond A. ^{[39
,40
]}

Swerdlow, Russell H. ^{[41
,42
,43
]}

Will, Yvonne ^{[44
]}

Ying, Zheng ^{[45
,46
]}

Joselin, Alvin ^{[38
]}

Gioran, Anna ^{[47
]}

Pinho, Catarina Moreira ^{[48
]}

Watters, Orla ^{[1
]}

Salvucci, Manuela ^{[1
]}

Llorente-Folch, Irene ^{[1
]}

Park, David S. ^{[38
]}

Bano, Daniele ^{[47
]}

Ankarcrona, Maria ^{[48
]}

Pizzo, Paola ^{[2
,5
]}

Prehn, Jochen H. M. ^{[1
]}

机构：

[1] Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Dublin, Ireland

[2] Univ Padua, Dept Biomed Sci, Padua, Italy

[3] Semmelweis Univ, Dept Med Biochem, Budapest, Hungary

[4] Louisiana State Univ Hlth New Orleans, Sch Med, Neurosci Ctr Excellence, New Orleans, LA 70112 USA

[5] CNR, Natl Res Council, Neurosci Inst, Padua, Italy

[6] Univ Salamanca, CIBERFES, Inst Funct Biol & Genom IBFG, CSIC, Salamanca, Spain

[7] Univ Marburg, Inst Pharmacol & Clin Pharm, D-35043 Marburg, Germany

[8] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat & Stem Cell Programs, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[10] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[11] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[12] Diana Helis Henry Med Res Fdn, Adrienne Helis Malvin Med Res Fdn, New Orleans, LA 70130 USA

[13] Univ N Carolina, Neurosci Ctr, Chapel Hill, NC USA

[14] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England

[15] UCL, Consortium Mitochondrial Res, London WC1E 6BT, England

[16] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA

[17] Univ Maryland, Sch Med, Ctr Shock Trauma & Anesthesiol Res STAR, Baltimore, MD 21201 USA

[18] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA

[19] Complejo Hosp Univ Albacete, Unidad Neuropsicofarmacol Translac, Albacete, Spain

[20] Univ Edinburgh, Edinburgh Med Sch, UK Dementia Res Inst, Edinburgh EH8 9XD, Midlothian, Scotland

[21] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[22] Univ Mississippi, Dept Biol, University, MS 38677 USA

[23] Yale Univ, Dept Internal Med, Sect Endocrinol, New Haven, CT USA

[24] Univ Castilla La Mancha, Dept Med Sci Pharmacol, Albacete, Spain

[25] Scripps Res Inst, Neurosci Translat Ctr, La Jolla, CA 92037 USA

[26] Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA

[27] Scripps Res Inst, Dept Neurosci, La Jolla, CA 92037 USA

[28] Scintillon Inst, Neurodegenerat Dis Ctr, San Diego, CA 92121 USA

[29] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA

[30] Weill Cornell Med, Brain & Mind Res Inst, New York, NY 10065 USA

[31] NIA, Intramural Res Program, Baltimore, MD 21224 USA

[32] Vanderbilt Univ, Sch Med, Dept Neurol, Nashville, TN 37212 USA

[33] Univ Med Ctr Mainz, Dept Neurol, Mainz, Germany

[34] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92093 USA

[35] Univ Cambridge, MRC Mitochondrial Biol Unit, Cambridge Biomed Campus, Cambridge CB2 0XY, England

[36] Buck Inst Res Aging, Novato, CA 94945 USA

[37] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Dept Biol Mol, E-28049 Madrid, Spain

[38] Univ Ottawa, Brain & Mind Res Inst, Ottawa, ON K1H 8M5, Canada

[39] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA

[40] San Francisco VA Med Ctr, San Francisco, CA 94121 USA

[41] Univ Kansas, Alzheimers Dis Ctr, Kansas City, KS 66160 USA

[42] Univ Kansas, Med Ctr, Dept Neurol Mol & Integrat Physiol, Kansas City, KS 66160 USA

[43] Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA

[44] Pfizer, Groton, CT 06340 USA

[45] Soochow Univ, Lab Cellular & Mol Neuropharmacol, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215021, Jiangsu, Peoples R China

[46] Soochow Univ, Coll Pharmaceut Sci, Suzhou 215021, Jiangsu, Peoples R China

[47] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[48] Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden

来源：

CELL DEATH AND DIFFERENTIATION | 2018年 / 25卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 爱尔兰科学基金会;

关键词：

ENCODED FLUORESCENT INDICATOR; OXYGEN SPECIES MEASUREMENT; LIVING CELLS; ALZHEIMERS-DISEASE; INTRACELLULAR PH; RESPIRATION MAINTAINS; SUPEROXIDE-PRODUCTION; CEREBELLAR NEURONS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS;

D O I：

10.1038/s41418-017-0020-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：542 / 572

页数：31

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