rain
Dissecting neuronal susceptibility to mitochondrial disease

Quintana Lab

WELCOME

Research

Saving neurons from mitochondrial disease one ATP at a time

Research overview

The Quintana lab investigates the molecular mechanisms defining why some neuronal populations are particularly affected by mitochondrial disease, with the overarching goal of identifying novel targets that lead to improved treatments for mitochondrial disease patients.

Dissecting neuronal susceptibility to mitochondrial disease

Mitochondria are the powerhouses of the cell. Mutations that render mitochondria unable to generate energy cause a group of rare and usually fatal pathologies collectively known as mitochondrial disease. It has been estimated that 1 in 5000 children in the US will develop a mitochondrial disease. Currently, there is no cure for mitochondrial disease and the treatments available are mostly ineffective. Energy-demanding cells such as neurons are especially sensitive to mitochondrial disease, and they account for most of the clinical signs and symptoms observed in humans, such as hypotonia, ataxia, seizures and early death. However, even if every single cell in the body carries the mutation, only specific brain areas seem to be affected by the deficiency. The Quintana lab current research focuses on identifying the neuronal populations susceptible to mitochondrial disease and which mechanisms are making these neurons die. This knowledge is essential to understand and fight these incurable diseases. The Quintana lab uses a wide array of approaches, combining molecular biology, stereotaxic surgery, mouse genetics and behavior, biochemistry, histology, optogenetics and in vivo electrophysiology to reveal novel pathways and mechanisms in neuronal function and pathology and open new and unexplored lines of research and therapeutic targets to treat mitochondrial disease encephalopathy.

funding

“EVERY SINGLE CELL RELIES ON MITOCHONDRIA TO SURVIVE.

1 IN 5000 CHILDREN ARE AFFECTED BY MITOCHONDRIAL DISEASE”

Current Projects

Recent Publications

Sharing our findings to advance knowledge

Chen B, Hui J, Montgomery KS, Gella A, Bolea I, Sanz E, Palmiter RD, Quintana A. 2017. Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome. Front Mol Neurosci. 10:265

Rainwater A, Sanz E, Palmiter RD, Quintana A. 2017. Striatal GPR88 Modulates Foraging Efficiency. J Neurosci. 37(33):7939-7947

Zimin PI, Woods CB, Quintana A, Ramirez JM, Morgan PG, Sedensky MM. 2016. Glutamatergic Neurotransmission Links Sensitivity to Volatile Anesthetics with Mitochondrial Function. Curr Biol. 26(16):2194-201.

Padilla SL, Qiu J, Soden ME, Sanz E, Nestor CC, Barker FD, Quintana A, Zweifel LS, Rønnekleiv OK, Kelly MJ, Palmiter RD. 2016. Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state. Nat Neurosci. 19(5):734-41. Cover Article and Featured in News and Views in Nature Neuroscience

Piroli GG, Manuel AM, Clapper AC, Walla MD, Baatz JE, Palmiter RD, Quintana A, Frizzell N. 2016. Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome. Mol Cell Proteomics. 15(2):445-61.

Sanz E, Quintana A, Deem JD, Steiner RA, Palmiter RD, McKnight GS. 2015. Fertility-regulating Kiss1 neurons arise from hypothalamic POMC-expressing progenitors. J Neurosci. 35(14):5549-56

Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. 2015.Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration. Cell.  160(1-2):177-90

Navia B, Ferrer B, Giralt M, Comes G, Carrasco J, Molinero A, Quintana A, Leclerc J, Viollet B, Señarís RM, Hidalgo J. 2014.Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice. Acta Physiol. 211(4):585-96.

Ferrer B, Navia B, Giralt M, Comes G, Carrasco J, Molinero A, Quintana A, Señarís RM, Hidalgo J.
2014. Muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner. Brain Behav Immun. pii: S0889-1591(14)00067-1

Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, Uhde L, Hui J, Wall VZ, Gagnidze A, Oh K, Wasko BM, Ramos FJ, Palmiter RD, Rabinovitch PS, Morgan PG, Sedensky MM, Kaeberlein M. 2013. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science. 342(6165):1524-8. Featured in Science Express  and in Research Highlights in Nature Medicine and Nature Reviews Neurology

Sanz E, Evanoff R, Quintana A, Evans E, Miller JA, Ko C, Amieux PS, Griswold MD, McKnight GS. 2013. RiboTag analysis of actively translated mRNAs in Sertoli and Leydig cells in vivo. PLoS ONE 8(6):e66179

Giralt M, Ramos R, Quintana A, Ferrer B, Erta M, Castro-Freire M, Comes G, Sanz E, Unzeta M, Pifarré P, García A, Campbell IL, Hidalgo J. 2013 Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. GLIA 61(4):587-600

Quintana A, Erta M, Ferrer B, Comes G, Giralt M, Hidalgo J. 2013. Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior. Brain Behav Immun. 27(1):162-173

Arnett AL, Beutler L, Quintana A, Allen J, Finn E, Palmiter RD, Chamberlain JS. 2013. Heparin-binding influences tissue tropism of AAV1 and AAV6 and increases efficiency of striated muscle transduction in mice. Gene Therapy 20(5):497-503

Quintana A, Morgan PG, Kruse SE, Palmiter RD, Sedensky MM. 2012 Altered Anesthetic Sensitivity of Mice Lacking Ndufs4, a Subunit of Mitochondrial Complex I. PLoS One 7(8):e42904

Quintana A, Zanella S, KochH, KruseSE, LeeD,Ramirez JM,  Palmiter RD. 2012. Fatal breathing dysfunction in a mouse model of Leigh Syndrome. Journal Clin Invest 122(7):2359-68.

Quintana A, Sanz E,Wang W, Storey GP, Güler AD, Wanat MJ, Roller BA, La Torre A, Amieux PS, McKnight GS, Bamford NS, Palmiter RD. 2012 Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors. Nat Neurosci. 15(11):1547-5. Cover Article and Featured in News and Views in Nature Neuroscience

Beutler LR, Wanat MJ, Quintana A, Sanz E, Bamford NS, Zweifel LS, Palmiter RD. 2011.Balanced NMDA receptor activity in Dopamine D1 Receptor (D1R)- and D2R-expressing medium spiny neurons is required for amphetamine sensitization. Proc Natl Acad Sci USA 108:4206-4211.

Bruchas MR,Schindler A, Shankar H, Messinger D, Miyatake M, Land BL, Lemos JC, Hagan C, Neumaier J, Quintana A,  Palmiter RD, Chavkin C. 2011. Selective p38 (alpha) MAPK deletion in serotonergic neurons produces stress-resilience in models of depression and addiction. Neuron. 71(3):498-511

Beutler LR, Eldred KC, Quintana A, Keene CD, Rose SE, Postupna N, Montine TJ, Palmiter RD. 2011 Severely impaired learning and altered neuronal morphology in mice lacking NMDA receptors in medium spiny neurons. PLoS One. (11):e28168

Quintana A, Kruse SE, Kapur RP, Sanz E, Palmiter RD. 2010. Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome.Proc Natl Acad Sci USA. 107:10996-1001. Cover Article

Quintana A, Müller M, Frausto RF, Ramos R, Getts DR, Sanz E, Hofer MJ, Krauthausen M, King NJ, Hidalgo J, Campbell IL. 2009. Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis..  J Immunol. 183:2079-88.

 

Complete Publication List (PubMed)

Public Engagement

Giving back to the community and spreading awareness of mitochondrial disease

Finding a cure for mitochondrial disease requires a constant dialogue and synergies between basic researchers, clinicians and the community. Raising public awareness and promoting education for mitochondrial disease is vital to advance in our knowledge on the pathogenesis and treatment of mitochondrial disease.

The determined efforts of countless individuals, associations and foundations,  have greatly, and positively, impacted mitochondrial research in many levels ranging from providing the perfect environment for mitochondrial researchers to thrive to promoting changes in governmental funding agencies. Among these organizations, we would like to acknowledge  the invaluable contributions of the United Mitochondrial Disease Foundation (UMDF) and the North-West Mitochondrial Research Guild in promoting mitochondrial disease research and education at a national/worldwide or local level, respectively, in the USA and AEPMI and the Fundación Mencía, in Spain.

 

UMDF NW MITO GUILD AEPMI FUNDACIÓN MENCÍA

 

The Quintana lab is committed to help  increase  public engagement and awareness of mitochondrial disease by ensuring the spread of our research by providing short summaries of key research papers and other developments in our blog and gallery, by participating in public seminars and by interacting with in local, national and international associations in meetings and community-oriented events.

 

“RAISING PUBLIC AWARENESS,

PROMOTING RESEARCH

 CREATING SYNERGIES.

THAT IS THE PATH TO FIND THE CURE FOR MITOCHONDRIAL DISEASE”

Members

Giving our 150% to find a cure to mitochondrial disease

Albert Quintana, PhD

Albert Quintana, PhD

Principal Investigator

Ramón y Cajal Investigator
Institut de Neurociències
Dept. Biologia Cel·lular, Fisiologia i Immunologia
Universitat Autònoma de Barcelona
CV
ResearchGate

albert.quintana@uab.cat

Elisenda Sanz, PhD

Elisenda Sanz, PhD

Senior Postdoctoral Researcher

Institut de Neurociències
Dept. Biologia Cel·lular, Fisiologia i Immunologia
Universitat Autònoma de Barcelona
CV

elisenda.sanz@uab.cat

Irene Bolea, PhD

Irene Bolea, PhD

Juan de la Cierva Postdoctoral Fellow

Institut de Neurociències
Universitat Autònoma de Barcelona
CV

irene.bolea@uab.cat

Alex Gella, PhD

Alex Gella, PhD

Marie Curie COFUND fellow

Institut de Neurociències
Universitat Autònoma de Barcelona
CV ResearchGate

alex.gella@uab.cat

Patricia Prada

Patricia Prada

Graduate Student

Institut de Neurociències
Universitat Autònoma de Barcelona

patricia.prada@uab.cat

Pablo Machuca

Pablo Machuca

Graduate Student

Institut de Neurociències
Universitat Autònoma de Barcelona

pablo.machuca@uab.cat

Andrea Urpí,

Andrea Urpí,

Graduate Student

Institut de Neurociències
Universitat Autònoma de Barcelona

andrea.urpi@uab.cat

Kelsey Montgomery

Kelsey Montgomery

Research Technician

Institut de Neurociències
Universitat Autònoma de Barcelona

kelsey.montgomery@uab.cat

Albert Quintana, PhD

Albert Quintana, PhD

Principal Investigator

Ramón y Cajal Investigator
Institut de Neurociències
Dept. Biologia Cel·lular, Fisiologia i Immunologia
Universitat Autònoma de Barcelona
CV
ResearchGate

albert.quintana@uab.cat

Elisenda Sanz, PhD

Elisenda Sanz, PhD

Senior Postdoctoral Researcher

Institut de Neurociències
Dept. Biologia Cel·lular, Fisiologia i Immunologia
Universitat Autònoma de Barcelona
CV

elisenda.sanz@uab.cat

Irene Bolea, PhD

Irene Bolea, PhD

Juan de la Cierva Postdoctoral Fellow

Institut de Neurociències
Universitat Autònoma de Barcelona
CV

irene.bolea@uab.cat

Alex Gella, PhD

Alex Gella, PhD

Marie Curie COFUND fellow

Institut de Neurociències
Universitat Autònoma de Barcelona
CV ResearchGate

alex.gella@uab.cat

Patricia Prada

Patricia Prada

Graduate Student

Institut de Neurociències
Universitat Autònoma de Barcelona

patricia.prada@uab.cat

Pablo Machuca

Pablo Machuca

Graduate Student

Institut de Neurociències
Universitat Autònoma de Barcelona

pablo.machuca@uab.cat

Andrea Urpí,

Andrea Urpí,

Graduate Student

Institut de Neurociències
Universitat Autònoma de Barcelona

andrea.urpi@uab.cat

Kelsey Montgomery

Kelsey Montgomery

Research Technician

Institut de Neurociències
Universitat Autònoma de Barcelona

kelsey.montgomery@uab.cat

ALONE WE CAN DO SO LITTLE,

TOGETHER WE CAN DO SO MUCH

Helen Keller

Alumni

Once Quintana lab always Quintana lab

Jessica Hui

Jessica Hui

Undergraduate Student

Alumni 2013-2015
Seattle Children’s Research Institute

Benjamin Bauer

Benjamin Bauer

Undergraduate Student

Alumni 2014
Seattle Children’s Research Institute

Jessica Hui

Jessica Hui

Undergraduate Student

Alumni 2013-2015
Seattle Children’s Research Institute

Benjamin Bauer

Benjamin Bauer

Undergraduate Student

Alumni 2014
Seattle Children’s Research Institute

LAB OPENINGS

There are no current openings in the lab at this moment.

 

Gallery

A taste of all our activities and events is just one click away

Neurons

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A Golgi-Cox staining of mouse cerebellum… 100-year old technique providing amazing labeling of brain cells

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A closeup of a cerebellar Purkinje neuron in an Ndufs4KO mice

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Microglial (green) and astroglial (red) reactivity observed in the vestibular and cerebellar lesions of an Ndufs4KO mouse

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Microglial (green) and astroglial and radial glial (red) activation in the cerebellum of an Ndufs4KO mouse.

Activated (green) and phagocytic (red) microglial cells surround a lesion in the vestibular nucleus of an Ndufs4KO mice.

Activated (green) and phagocytic (red) microglial cells surround a lesion in the vestibular nucleus of an Ndufs4KO mice.

 

Mitochondria

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Red fluorescent mitochondria waiting to be purified. Cell nuclei in blue.

Green fluorescent mitochondria in a HEK cell

Green fluorescent mitochondria in a HEK cell

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A close-up of red fluorescent mitochondria in a HEK cell

Mito Science Night

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Eli demonstrating how to fluorescently label mitochondria

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Nicole explaining green fluorescent worms

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Bernhard demonstrating how the Seahorse analyzes mitochondrial respiration

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A fuzzy stormtrooper mouse is discovering optogenetics

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Jill and Ed are fully gowned for surgery!

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We are ready! 🙂

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Christian is ready to show how an electrophysiological trace looks!