Defective mitochondrial function and motility due to mitofusin 1 overexpression in insulin secreting cells

Kyusang Park, Andreas Wiederkehr, Claes B. Wollheim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal β-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

Original languageEnglish
Pages (from-to)71-77
Number of pages7
JournalKorean Journal of Physiology and Pharmacology
Volume16
Issue number1
DOIs
Publication statusPublished - 2012 Feb 1

Fingerprint

Insulin-Secreting Cells
Mitochondria
Mitochondrial Dynamics
Adenoviridae
Oligomycins
Doxycycline
Microtubules
Energy Metabolism
Cell Survival
Cell Membrane
Insulin
Glucose

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

Cite this

@article{caaeda2e7f36492286e7ab240499f6f6,
title = "Defective mitochondrial function and motility due to mitofusin 1 overexpression in insulin secreting cells",
abstract = "Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal β-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.",
author = "Kyusang Park and Andreas Wiederkehr and Wollheim, {Claes B.}",
year = "2012",
month = "2",
day = "1",
doi = "10.4196/kjpp.2012.16.1.71",
language = "English",
volume = "16",
pages = "71--77",
journal = "Korean Journal of Physiology and Pharmacology",
issn = "1226-4512",
publisher = "Korean Physiological Soc. and Korean Soc. of Pharmacology",
number = "1",

}

Defective mitochondrial function and motility due to mitofusin 1 overexpression in insulin secreting cells. / Park, Kyusang; Wiederkehr, Andreas; Wollheim, Claes B.

In: Korean Journal of Physiology and Pharmacology, Vol. 16, No. 1, 01.02.2012, p. 71-77.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Defective mitochondrial function and motility due to mitofusin 1 overexpression in insulin secreting cells

AU - Park, Kyusang

AU - Wiederkehr, Andreas

AU - Wollheim, Claes B.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal β-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

AB - Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal β-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

UR - http://www.scopus.com/inward/record.url?scp=84858670473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858670473&partnerID=8YFLogxK

U2 - 10.4196/kjpp.2012.16.1.71

DO - 10.4196/kjpp.2012.16.1.71

M3 - Article

VL - 16

SP - 71

EP - 77

JO - Korean Journal of Physiology and Pharmacology

JF - Korean Journal of Physiology and Pharmacology

SN - 1226-4512

IS - 1

ER -