Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism

By D. Bach, S. Pich, Francesc X. Soriano, N. Véga, Bernhard Baumgartner, J. Oriola, J. Daugaard, J. Lloberas, M. Camps, J. Zierath and 8 more. Journal of Biological Chemistry, 2003

832 citations recorded by the source corpus.

In many cells and specially in muscle, mitochondria form elongated filaments or a branched reticulum. We show that Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, is induced during myogenesis and contributes to the maintenance and operation of the mitochondrial network. Repression of Mfn2 caused morphological and functional fragmentation of the mitochondrial network into independent clusters. Concomitantly, repression of Mfn2 reduced glucose oxidation, mitochondrial membrane potential, cell respiration, and mitochondrial proton leak. We also show that the Mfn2-dependent mechanism of mitochondrial control is disturbed in obesity by reduced Mfn2 expression. In all, our data indicate that Mfn2 expression is crucial in mitochondrial metabolism through the maintenance of the mitochondrial network architecture, and reduced Mfn2 expression may explain some of the metabolic alterations associated with obesity.

Subfields: Clinical Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/08732bec917e2657561248137ac8ace3d471b831

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In Clinical Biochemistry

1. Orian Shirihai
2. M. Duchen
3. G. Perkins
4. Wen Chen
5. Yongsheng Li
6. V. Veksler
7. Reem M. Sallam
8. A. B. Knott

In Molecular Biology

1. Orian Shirihai
2. M. Duchen
3. M. Palacín
4. G. Perkins
5. Wen Chen
6. Yongsheng Li
7. V. Veksler
8. Antonio Zorzano

In Physiology

1. Orian Shirihai
2. M. Duchen
3. Reem M. Sallam
4. R. Schwarzenbacher
5. M. Liesa
6. A. Alfadda
7. E. Bossy‐Wetzel

Citations in the corpus

• Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. (2008, result): “This observation is in agreement with previous reports in other models of obesity and diabetes and also in humans (22).”
• Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. (2008, background): “Mitofusins are highly expressed in heart and skeletal muscle, and their expression is induced during myogenesis and physical exercise.(6,7) In addition to the control of the mitochondrial network, Mfn2 also stimulates the mitochondrial oxidation of substrates, cell respiration, and mitochondrial mem”
• Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010, neutral): “These processes depend on certain proteins, including two isoforms of mitofusin (MFN) involved in docking to initiate fusion and the presenillin-associated rhomboid-like (PARL) protein important for morphologic integrity (63).”
• The Molecular Bases of Training Adaptation (2007, neutral): “proteins have been strongly implicated (Bach et al. 2003; Santel et al. 2003).”
• Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “Interestingly, deletion of hepatic MFN2 signi fi cantly promotes in fl ammatory responses, accumulation of triglycerides, fi brosis, and HCC in mouse models of NASH, whereas restoring MFN2 expression using adenovirus in mutant (liver-speci fi c) mice lacking MFN2 observably alleviate disease symptoms of”
• Mitochondrial fragmentation in neurodegeneration (2008, background): “, and increased levels of MFN2 in developing muscle tissue correlates with more efficient mitochondrial function and energy transmission frm the cell periphery to the cell cor”
• Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure (2013, background): “An accompanying decrease in Mfn2 expression provided a potential mechanism to the reduction in mitochondrial size (Bach et al., 2003; Bach et al., 2005).”
• Mitochondrial dynamics in mammalian health and disease. (2009, background): “In these conditions, coupled oxygen consumption is unaltered, whereas respiration linked to the mitochondrial proton leak is significantly reduced in antisense cells (16).”
• Reactive Oxygen Species in Health and Disease (2012, background): “As an example, reduced expression of mitofusin 2 (Mfn2), one of the mitochondrial proteins responsible for its dynamic morphology, was demonstrated to be partly responsible for decreased glucose oxidation and cell respiration in obesity [49].”
• PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism (2020, background): “Indeed, reduced Mfn2 expression was described in obese type 2 diabetic patients, leading to functional and morphological fragmentation of the mitochondrial network [175].”
• Cellular and molecular mechanisms of mitochondrial function (2012, background): “50,51 Mice lacking either Mfn1 or Mfn2 die midgestation while embryonic stem cell lines derived from mice lack any detectable fusion activity highlighting the severity of the deletions.”