Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1

Rupali Vohra; Iswariyaraja Sridevi Gurubaran; Ulrik Henriksen; Linda Hildegaard Bergersen; Lene Juel Rasmussen; Claus Desler; Dorte Marie Skytt; Miriam Kolko

doi:10.1016/j.mito.2017.02.003

Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1

Mitochondrion. 2017 Sep:36:52-59. doi: 10.1016/j.mito.2017.02.003. Epub 2017 Feb 6.

Authors

Rupali Vohra¹, Iswariyaraja Sridevi Gurubaran², Ulrik Henriksen², Linda Hildegaard Bergersen³, Lene Juel Rasmussen⁴, Claus Desler⁵, Dorte Marie Skytt⁶, Miriam Kolko⁷

Affiliations

¹ University of Copenhagen, Department of Neuroscience and Pharmacology, Blegdamsvej 3B, Building 33.4.83, Copenhagen N, Denmark; University of Copenhagen, Department of Drug Design and Pharmacology, Universitetsparken 2, Building 22.4.405, 2100 Copenhagen Ø, Denmark; Zealand University Hospital, Department of Ophthalmology, Vestermarksvej 23, 4000 Roskilde, Denmark.
² University of Copenhagen, Department of Neuroscience and Pharmacology, Blegdamsvej 3B, Building 33.4.83, Copenhagen N, Denmark.
³ University of Copenhagen, Department of Neuroscience and Pharmacology, Blegdamsvej 3B, Building 33.4.83, Copenhagen N, Denmark; University of Copenhagen, Center for Healthy Aging, Blegdamsvej 3B, Building 18.1, 2200 Copenhagen N, Denmark; University of Oslo, Brain and Muscle Energy Group, Sognsvannsveien 10, 0316 Oslo, Norway.
⁴ University of Copenhagen, Center for Healthy Aging, Blegdamsvej 3B, Building 18.1, 2200 Copenhagen N, Denmark.
⁵ Zealand University Hospital, Department of Ophthalmology, Vestermarksvej 23, 4000 Roskilde, Denmark.
⁶ University of Copenhagen, Department of Neuroscience and Pharmacology, Blegdamsvej 3B, Building 33.4.83, Copenhagen N, Denmark; University of Copenhagen, Department of Drug Design and Pharmacology, Universitetsparken 2, Building 22.4.405, 2100 Copenhagen Ø, Denmark.
⁷ University of Copenhagen, Department of Neuroscience and Pharmacology, Blegdamsvej 3B, Building 33.4.83, Copenhagen N, Denmark; University of Copenhagen, Department of Drug Design and Pharmacology, Universitetsparken 2, Building 22.4.405, 2100 Copenhagen Ø, Denmark; Zealand University Hospital, Department of Ophthalmology, Vestermarksvej 23, 4000 Roskilde, Denmark. Electronic address: mkolko@dadlnet.dk.

PMID: 28185966
DOI: 10.1016/j.mito.2017.02.003

Abstract

Using the human Müller cell line, MIO-M1, the aim was to study the impact of mitochondrial inhibition in Müller glia through antimycin A treatment. MIO-M1 cell survival, levels of released lactate, mitochondrial function, and glutamate uptake were studied in response to mitochondrial inhibition and glucose restriction. Lactate release decreased in response to glucose restriction. Combined glucose restriction and blocked mitochondrial activity decreased survival and caused collapse of the respiratory chain measured by oxygen consumption rate and extracellular acidification rate. Mitochondrial inhibition caused impaired glutamate uptake and decreased mRNA expression of the glutamate transporter, EAAT1. Over all, we show important roles of mitochondrial activity in MIO-M1 cell function and survival.

Keywords: Antimycin A; Glutamate; Lactate; MIO-M1 cell line; Mitochondria; Müller cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Infective Agents / metabolism
Antimycin A / metabolism
Biological Transport
Cell Line
Cell Survival / drug effects
Ependymoglial Cells / drug effects
Ependymoglial Cells / metabolism*
Glucose / metabolism
Glutamic Acid / metabolism*
Humans
Lactates / metabolism
Mitochondria / drug effects
Mitochondria / metabolism*

Substances

Anti-Infective Agents
Lactates
Glutamic Acid
Antimycin A
Glucose