Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 5523-5528 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 109 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 2012 |
| MoE publication type | A4 Article in a conference publication |
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Keywords
- mitochondrial dynamics
- insulin resistance
- metabolism
- oxidative stress
Cite this
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Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. / Sebastián, David; Hernández-Alvarez, María Isabel; Segalés, Jessica; Sorianello, Eleanora; Muñoz, Juan Pablo; Sala, David; Waget, Aurélie; Liesa, Marc; Paz, José C.; Gopalacharyulu, Peddinti; Orešič, Matej; Pich, Sara; Burcelin, R.; Palacín, Manuel; Zorzano, Antonio (Corresponding Author).
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 14, 2012, p. 5523-5528.Research output: Contribution to journal › Article in a proceedings journal › Scientific › peer-review
TY - JOUR
T1 - Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis
AU - Sebastián, David
AU - Hernández-Alvarez, María Isabel
AU - Segalés, Jessica
AU - Sorianello, Eleanora
AU - Muñoz, Juan Pablo
AU - Sala, David
AU - Waget, Aurélie
AU - Liesa, Marc
AU - Paz, José C.
AU - Gopalacharyulu, Peddinti
AU - Orešič, Matej
AU - Pich, Sara
AU - Burcelin, R.
AU - Palacín, Manuel
AU - Zorzano, Antonio
PY - 2012
Y1 - 2012
N2 - Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2 diabetic patients. Here, we provide in vivo evidence that Mfn2 plays an essential role in metabolic homeostasis. Liver-specific ablation of Mfn2 in mice led to numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency impaired insulin signaling in liver and muscle. Furthermore, Mfn2 deficiency was associated with endoplasmic reticulum stress, enhanced hydrogen peroxide concentration, altered reactive oxygen species handling, and active JNK. Chemical chaperones or the antioxidant N-acetylcysteine ameliorated glucose tolerance and insulin signaling in liver-specific Mfn2 KO mice. This study provides an important description of a unique unexpected role of Mfn2 coordinating mitochondria and endoplasmic reticulum function, leading to modulation of insulin signaling and glucose homeostasis in vivo.
AB - Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2 diabetic patients. Here, we provide in vivo evidence that Mfn2 plays an essential role in metabolic homeostasis. Liver-specific ablation of Mfn2 in mice led to numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency impaired insulin signaling in liver and muscle. Furthermore, Mfn2 deficiency was associated with endoplasmic reticulum stress, enhanced hydrogen peroxide concentration, altered reactive oxygen species handling, and active JNK. Chemical chaperones or the antioxidant N-acetylcysteine ameliorated glucose tolerance and insulin signaling in liver-specific Mfn2 KO mice. This study provides an important description of a unique unexpected role of Mfn2 coordinating mitochondria and endoplasmic reticulum function, leading to modulation of insulin signaling and glucose homeostasis in vivo.
KW - mitochondrial dynamics
KW - insulin resistance
KW - metabolism
KW - oxidative stress
U2 - 10.1073/pnas.1108220109
DO - 10.1073/pnas.1108220109
M3 - Article in a proceedings journal
VL - 109
SP - 5523
EP - 5528
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 14
ER -