Nicotine Modulates Mitochondrial Dynamics in Hippocampal Neurons

  • Juan A. Godoy
  • Angel G. Valdivieso
  • Nibaldo C. Inestrosa


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.


Neurons Nicotine Mitochondrial dynamics Dpr1 PGC-1α 



adenosine triphosphate


AMP-activated protein kinase


endoplasmic reticulum


mitofusin 2


cytosine arabinoside


phosphate-buffered saline


phosphate-buffered saline/calcium magnesium


bovine serum albumin


days in vitro


standard error of the mean


inositol 1,4,5-trisphosphate receptor


optic atrophy 1


dynamin-related protein 1


peroxisome proliferator-activated receptor γ co-activator 1α


reactive oxygen species


mitochondrial membrane potential




dihydro-β-erythroidine hydrobromide


corrected total cell fluorescence


nicotinic acetylcholine receptor


alpha7-nicotinic acetylcholine receptor




Alzheimer’s disease


Wingless/integration site


electron transport chain


mitochondrial complex I




mitochondrial permeability transition pore


mitochondrial division inhibitor 1


nicotinamide adenine dinucleotide


cytochrome b




ryanodine receptor


sarco/endoplasmic reticulum Ca+2-ATPase


mitochondrial rho GTPase

TOM 20

translocase of outer mitochondrial membrane 20


voltage-dependent anion channel


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.

Funding Information

This work was supported by grants AFB 170005 and CONICYT-PFB 12/2007 from the Basal Centre for Excellence in Science and Technology (CARE UC) and FONDECYT 1160724, both to NCI. JAG is a PhD student at Universitat Pompeu Fabra, Barcelona, Spain. AGV was supported by a Santander Río Ibero-American fellowship through UC and PICT-2015-1031 from the National Scientific and Technical Research Council of Argentina (CONICET).

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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