Nicotine Modulates Mitochondrial Dynamics in Hippocampal Neurons

  • Juan A. Godoy
  • Angel G. Valdivieso
  • Nibaldo C. Inestrosa
Article
  • 128 Downloads

Abstract

Mitochondria are widely recognized as fundamental organelles for cellular physiology and constitute the main energy source for different cellular processes. The location, morphology, and interactions of mitochondria with other organelles, such as the endoplasmic reticulum (ER), have emerged as critical events capable of determining cellular fate. Mitochondria-related functions have proven particularly relevant in neurons; mitochondria are necessary for proper neuronal morphogenesis and the highly energy-demanding synaptic transmission process. Mitochondrial health depends on balanced fusion-fission events, termed mitochondrial dynamics, to repair damaged organelles and/or improve the quality of mitochondrial function, ATP production, calcium homeostasis, and apoptosis, which represent some mitochondrial functions closely related to mitochondrial dynamics. Several neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, have been correlated with severe mitochondrial dysfunction. In this regard, nicotine, which has been associated with relevant neuroprotective effects mainly through activation of the nicotinic acetylcholine receptor (nAChR), exerts its effects at least in part by acting directly on mitochondrial physiology and morphology. Additionally, a recent description of mitochondrial nAChR localization suggests a nicotine-dependent mitochondrial function. In the present work, we evaluated in cultured hipocampal neurons the effects of nicotine on mitochondrial dynamics by assessing mitochondrial morphology, membrane potential, as well as interactions between mitochondria, cytoskeleton and IP3R, levels of the cofactor PGC-1α, and fission-fusion-related proteins. Our results suggest that nicotine modulates mitochondrial dynamics and influences mitochondrial association from microtubules, increasing IP3 receptor clustering showing modulation between mitochondria-ER communications, together with the increase of mitochondrial biogenesis.

Keywords

Neurons Nicotine Mitochondrial dynamics Dpr1 PGC-1α 

Abbreviations

ATP

adenosine triphosphate

AMPK

AMP-activated protein kinase

ER

endoplasmic reticulum

MFN2

mitofusin 2

AraC

cytosine arabinoside

PBS

phosphate-buffered saline

PBSCAM

phosphate-buffered saline/calcium magnesium

BSA

bovine serum albumin

DIV

days in vitro

SEM

standard error of the mean

IP3R

inositol 1,4,5-trisphosphate receptor

OPA1

optic atrophy 1

DRP1

dynamin-related protein 1

PGC-1α

peroxisome proliferator-activated receptor γ co-activator 1α

ROS

reactive oxygen species

mΔΨ

mitochondrial membrane potential

α-Btx

alpha-bungarotoxin

DHβE

dihydro-β-erythroidine hydrobromide

CTCF

corrected total cell fluorescence

nAChR

nicotinic acetylcholine receptor

α7-AChR

alpha7-nicotinic acetylcholine receptor

ACh

acetylcholine

AD

Alzheimer’s disease

Wnt

Wingless/integration site

ETC

electron transport chain

mCx-I

mitochondrial complex I

MFN2

mitofusin2

mPTP

mitochondrial permeability transition pore

Mdivi-1

mitochondrial division inhibitor 1

NADH

nicotinamide adenine dinucleotide

Mt-cyb

cytochrome b

MTs

microtubules

RyR

ryanodine receptor

SERCA

sarco/endoplasmic reticulum Ca+2-ATPase

MIRO

mitochondrial rho GTPase

TOM 20

translocase of outer mitochondrial membrane 20

VDAC

voltage-dependent anion channel

Notes

Author Contributions

JAG conceived and conducted most of the experiments with mitochondria, analyzed the results and wrote most of the article. AGV conducted the western blot experiments, analyzed the results and wrote the article. NCI conceived the general idea for the project and wrote the article.

Compliance with Ethical Standards

Conflict of Interest

All authors declare no conflicts of interest related to the contents of this article.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Juan A. Godoy
    • 1
    • 2
  • Angel G. Valdivieso
    • 3
  • Nibaldo C. Inestrosa
    • 1
    • 2
    • 4
    • 5
  1. 1.Centro de Envejecimiento y Regeneración (CARE UC); Departamento de Biología Celular y Molecular; Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  2. 2.Centro de Excelencia en Biomedicina de Magallanes (CEBIMA)Universidad de MagallanesPunta ArenasChile
  3. 3.Institute for Biomedical Research (BIOMED), Laboratory of Cellular and Molecular Biology, School of Medical SciencesPontifical Catholic University of Argentina (UCA) and The National Scientific and Technical Research Council of Argentina (CONICET)Buenos AiresArgentina
  4. 4.Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of MedicineUniversity of New South WalesSydneyAustralia
  5. 5.(CARE UC) Biomedical CenterPontificia Universidad Católica de ChileSantiagoChile

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