Defective Mitochondrial Function and Motility Due to Mitofusin 1 Overexpression in Insulin Secreting Cells.
10.4196/kjpp.2012.16.1.71
- Author:
Kyu Sang PARK
1
;
Andreas WIEDERKEHR
;
Claes B WOLLHEIM
Author Information
1. Department of Physiology, Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju 220-701, Korea. qsang@yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Mitochondrial fusion;
Mitofusin 1;
Mitochondrial function;
Mitochondrial motility;
Insulin secretion
- MeSH:
Adenoviridae;
Animals;
Cell Membrane;
Cell Survival;
Cytosol;
Energy Metabolism;
Insulin;
Insulin-Secreting Cells;
Luminescent Proteins;
Mitochondria;
Mitochondrial Dynamics;
Rats
- From:The Korean Journal of Physiology and Pharmacology
2012;16(1):71-77
- CountryRepublic of Korea
- Language:English
-
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 beta-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.
