MFN2

File:6JFL PDB.png of the Mitofusin-2 protein (rainbow colored, N-terminus = blue, C-terminus = red).{{PDB|6JFL}}; {{cite journal | vauthors = Li YJ, Cao YL, Feng JX, Qi Y, Meng S, Yang JF, Zhong YT, Kang S, Chen X, Lan L, Luo L, Yu B, Chen S, Chan DC, Hu J, Gao S | title = Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset | journal = Nature Communications | volume = 10 | issue = 1 | pages = 4914 | date = October 2019 | pmid = 31664033 | pmc = 6820788 | doi = 10.1038/s41467-019-12912-0 | bibcode = 2019NatCo..10.4914L }}|upright=1.5]]

File:ProvaMFN2 animada.gif

The human mitofusin-2 protein contains 757 amino acid residues. The MFN2 comprises a large cytosolic GTPase domain at the N-terminal, followed by a coiled-coil heptad-repeat (HR1) domain, a proline-rich (PR) region, two sequential transmembrane (TM) domains crossing the OMM and a second cytosolic heptad-repeat (HR2) domain at the C-terminal. MFN2 has been shown by electron microscopy (EM) to accumulate in contact regions between adjacent mitochondria, supporting their role in mitochondrial fusion.{{cite journal | vauthors = Rojo M, Legros F, Chateau D, Lombès A | title = Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo | journal = Journal of Cell Science | volume = 115 | issue = Pt 8 | pages = 1663–74 | date = April 2002 | doi = 10.1242/jcs.115.8.1663 | pmid = 11950885 }}{{cite journal | vauthors = Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT | title = Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells | journal = Journal of Cell Science | volume = 116 | issue = Pt 13 | pages = 2763–74 | date = July 2003 | pmid = 12759376 | doi = 10.1242/jcs.00479 | s2cid = 6661619 | doi-access = }} Seminal studies revealed that both, MFN1 and MFN2 spanning from the OMM of two opposing mitochondria, physically interact in trans, by the formation of antiparallel dimers between their HR2 domains.{{cite journal | vauthors = Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC | title = Structural basis of mitochondrial tethering by mitofusin complexes | journal = Science | volume = 305 | issue = 5685 | pages = 858–62 | date = August 2004 | pmid = 15297672 | doi = 10.1126/science.1099793 | bibcode = 2004Sci...305..858K | s2cid = 24595783 }}

A pivotal in vivo study revealed that MFN2 is essential for embryonic development,{{cite journal | vauthors = Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC | title = Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development | journal = The Journal of Cell Biology | volume = 160 | issue = 2 | pages = 189–200 | date = January 2003 | pmid = 12527753 | pmc = 2172648 | doi = 10.1083/jcb.200211046 }} thus, the deletion of MFN2 in mice is lethal during midgestation. The inactivation of MFN2 alleles after placentation also revealed that MFN2 ablation severely impairs cerebellum development.{{cite journal | vauthors = Chen H, McCaffery JM, Chan DC | title = Mitochondrial fusion protects against neurodegeneration in the cerebellum | journal = Cell | volume = 130 | issue = 3 | pages = 548–62 | date = August 2007 | pmid = 17693261 | doi = 10.1016/j.cell.2007.06.026 | s2cid = 1138255 | doi-access = free }} It has been also described that Mfn1 and Mfn2 are ubiquitously expressed yet they display different relative levels of expression between tissues, with MFN2 being the predominantly expressed mitofusin in the brain and MFN1 in the heart. This tissue-specific expression could be one of the reasons its ablation induces cerebellar-specific impairments.{{cite journal | vauthors = Filadi R, Pendin D, Pizzo P | title = Mitofusin 2: from functions to disease | journal = Cell Death & Disease | volume = 9 | issue = 3 | pages = 330 | date = February 2018 | pmid = 29491355 | pmc = 5832425 | doi = 10.1038/s41419-017-0023-6 }} 50px Text was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].

File:HYP NORM 38.jpg

MFN2 is a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network.{{cite web|title=Entrez Gene: MFN2 mitofusin 2|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9927}} Mitochondria function as a dynamic network constantly undergoing fusion and fission. The balance between fusion and fission is important in maintaining the integrity of the mitochondria and facilitates the mixing of the membranes and the exchange of DNA between mitochondria. MFN1 and MFN2 mediate outer membrane fusion, OPA1 is involved in inner membrane fusion, and DRP1 is responsible for mitochondrial fission.{{cite journal | vauthors = Chan DC | title = Dissecting mitochondrial fusion | journal = Developmental Cell | volume = 11 | issue = 5 | pages = 592–4 | date = November 2006 | pmid = 17084350 | doi = 10.1016/j.devcel.2006.10.009 | doi-access = free }}

Mitochondrial fusion is unique because it involves two membranes: the OMM and the inner mitochondrial membrane (IMM), that must be rearranged in a coordinated manner in order to maintain organelle integrity. Recent studies have shown that MFN2-deficient cells display an aberrant mitochondrial morphology, with a clear fragmentation of the network.

Mitochondrial fusion is essential for embryonic development. Knockout mice for either MFN1 or MFN2 have fusion deficits and die midgestation. MFN2 knockout mice die at embryonic day 11.5 due to a defect in the giant cell layer of the placenta. Mitochondrial fusion is also important for mitochondrial transport and localization in neuronal processes.{{cite journal | vauthors = Sheng ZH, Cai Q | title = Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration | journal = Nature Reviews. Neuroscience | volume = 13 | issue = 2 | pages = 77–93 | date = January 2012 | pmid = 22218207 | pmc = 4962561 | doi = 10.1038/nrn3156 }} Conditional MFN2 knockout mice show degeneration in the Purkinje cells of the cerebellum, as well as improperly localized mitochondria in the dendrites. MFN2 also associates with the MIRO-Milton complex which links the mitochondria to the kinesin motor.

MFN2 has also been suggested to be a key regulator of ER-mitochondria contiguity, though its exact function in this inter-organelle still remains unknown. Small fractions of MFN2 have been observed to be located in ER membranes, particularly in the so called ER mitochondria-associated membranes (MAM). Several processes known to take place at MAM, such as autophagosomes formation have been claimed to be modulated by the presence of MFN2.

MFN2 has been proposed to be essential for the transport of mitochondria along axons, being involved in their attachment to microtubules through interaction with the two main motor proteins Miro and Milton.{{cite journal | vauthors = Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH | title = Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex | journal = The Journal of Neuroscience | volume = 30 | issue = 12 | pages = 4232–40 | date = March 2010 | pmid = 20335458 | doi = 10.1523/jneurosci.6248-09.2010 | pmc = 2852190 }}

Other intracellular pathways, such as cell cycle progression, maintenance of mitochondrial bioenergetics, apoptosis, and autophagy, have been demonstrated to be modulated by MFN2.

The importance of a regulated mitochondrial morphology in cell physiology makes immediately clear the potential impact of MFN2 in the onset/progression of different pathological conditions.

Charcot-Marie-Tooth disease type 2A (CMT2A) is caused by mutations in the MFN2 gene. MFN2 mutations are linked to neurological disorders characterized by a wide clinical phenotype that involves the central and peripheral nervous system.{{cite journal | vauthors = Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, Hamilton SR, Van Stavern G, Krajewski KM, Stajich J, Tournev I, Verhoeven K, Langerhorst CT, de Visser M, Baas F, Bird T, Timmerman V, Shy M, Vance JM | display-authors = 6 | title = Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2 | journal = Annals of Neurology | volume = 59 | issue = 2 | pages = 276–81 | date = February 2006 | pmid = 16437557 | doi = 10.1002/ana.20797 | s2cid = 30679835 }}{{cite journal | vauthors = Vallat JM, Ouvrier RA, Pollard JD, Magdelaine C, Zhu D, Nicholson GA, Grew S, Ryan MM, Funalot B | display-authors = 6 | title = Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations | journal = Journal of Neuropathology and Experimental Neurology | volume = 67 | issue = 11 | pages = 1097–102 | date = November 2008 | pmid = 18957892 | doi = 10.1097/nen.0b013e31818b6cbc | s2cid = 16302093 | doi-access = }} The impairment of the former is rarer while neuropathy forms are more frequent and severe, involving both legs and arms, with weakness, sensory loss, and optical atrophy. All these complex phenotypes are clinically collected in the neurological disorder CMT2A, a subtype of a heterogeneous group of congenital neuromuscular diseases which affect motor and sensory neurons, called CMT disease.{{cite journal | vauthors = Cartoni R, Martinou JC | title = Role of mitofusin 2 mutations in the physiopathology of Charcot-Marie-Tooth disease type 2A | journal = Experimental Neurology | volume = 218 | issue = 2 | pages = 268–73 | date = August 2009 | pmid = 19427854 | doi = 10.1016/j.expneurol.2009.05.003 | s2cid = 9341454 | url = https://archive-ouverte.unige.ch/unige:18687 }}{{cite journal | vauthors = Barisic N, Claeys KG, Sirotković-Skerlev M, Löfgren A, Nelis E, De Jonghe P, Timmerman V | title = Charcot-Marie-Tooth disease: a clinico-genetic confrontation | journal = Annals of Human Genetics | volume = 72 | issue = Pt 3 | pages = 416–41 | date = May 2008 | pmid = 18215208 | doi = 10.1111/j.1469-1809.2007.00412.x | s2cid = 33405406 | doi-access = free }}

Among different cell types, neurons are particularly sensitive to MFN2 defects: to work properly, these cells need functional mitochondria located at specific sites to support adequate ATP production and Ca²⁺ buffering.{{cite journal | vauthors = Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R | title = Mitochondria, calcium and cell death: a deadly triad in neurodegeneration | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1787 | issue = 5 | pages = 335–44 | date = May 2009 | pmid = 19268425 | doi = 10.1016/j.bbabio.2009.02.021 | pmc = 2696196 }} A defective mitochondrial fusion has been suggested to participate in the pathogenesis of CMT2A. Another important cell feature altered in the presence of MFN2 mutations is mitochondrial transport and indeed current models propose this defect as the major cause of CMT2A.

Mutations in OPA1 also cause optic atrophy, which suggests a common role of mitochondrial fusion in neuronal dysfunction.{{cite journal | vauthors = Cartoni R, Martinou JC | title = Role of mitofusin 2 mutations in the physiopathology of Charcot-Marie-Tooth disease type 2A | journal = Experimental Neurology | volume = 218 | issue = 2 | pages = 268–73 | date = August 2009 | pmid = 19427854 | doi = 10.1016/j.expneurol.2009.05.003 | s2cid = 9341454 | url = https://archive-ouverte.unige.ch/unige:18687/ATTACHMENT01 }} The exact mechanism of how mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is evidence suggesting that it could be due to defects in the axonal transport of mitochondria.

Increasing evidence suggests a possible link between MFN2 deregulation and Alzheimer's disease (AD). In particular, MFN2 protein and mRNA levels are decreased in the frontal cortex of patients with AD,{{cite journal | vauthors = Manczak M, Calkins MJ, Reddy PH | title = Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage | journal = Human Molecular Genetics | volume = 20 | issue = 13 | pages = 2495–509 | date = July 2011 | pmid = 21459773 | doi = 10.1093/hmg/ddr139 | pmc = 3109997 }} as well as in hippocampal neurons of post-mortem AD patients.{{cite journal | vauthors = Chen Y, Han S, Huang X, Ni J, He X | title = The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice | journal = International Journal of Molecular Sciences | volume = 17 | issue = 2 | pages = 163 | date = January 2016 | pmid = 26828481 | doi = 10.3390/ijms17020163 | pmc = 4783897 | doi-access = free }} Notably, the cortex and hippocampus are the brain's areas in which a major neuronal impairment is observed in AD. Interestingly, the MFN2 gene is located on chromosome 1p36, which has been suggested to be an AD-associated locus.{{cite journal | vauthors = Hiltunen M, Mannermaa A, Thompson D, Easton D, Pirskanen M, Helisalmi S, Koivisto AM, Lehtovirta M, Ryynänen M, Soininen H | display-authors = 6 | title = Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland | journal = Neurology | volume = 57 | issue = 9 | pages = 1663–8 | date = November 2001 | pmid = 11706108 | doi = 10.1212/wnl.57.9.1663 | s2cid = 72375165 }} However, it is currently unknown whether MFN2 alterations are causative for the pathology or just a consequence of AD. In particular, it is not clear if MFN2 is linked to AD through its effects on mitochondria or by affecting other pathways.

In summary, mitochondrial dysfunction is a prominent feature of AD neurons. It has been described that levels of DRP1, OPA1, MFN1, and MFN2 are significantly reduced whereas levels of Fis1 are significantly increased in AD.{{cite journal | vauthors = Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X | title = Impaired balance of mitochondrial fission and fusion in Alzheimer's disease | journal = The Journal of Neuroscience | volume = 29 | issue = 28 | pages = 9090–103 | date = July 2009 | pmid = 19605646 | doi = 10.1523/JNEUROSCI.1357-09.2009 | pmc = 2735241 }}

MFN2 is a key substrate of the PINK1/parkin couple, whose mutations are linked to the familial forms of Parkinson's disease (PD). MFN2 has been demonstrated to be essential for axonal projections of midbrain dopaminergic (DA) neurons that are affected in PD.{{cite journal | vauthors = Lee S, Sterky FH, Mourier A, Terzioglu M, Cullheim S, Olson L, Larsson NG | title = Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons | journal = Human Molecular Genetics | volume = 21 | issue = 22 | pages = 4827–35 | date = November 2012 | pmid = 22914740 | doi = 10.1093/hmg/dds352 | doi-access = }} MFN2 alterations in the progression of PD, considering the capacity of PINK1 and parkin to trigger post-translational modifications in their substrates, have yet to be evaluated.

The MFN2 protein may play a role in the pathophysiology of obesity.{{cite journal | vauthors = Zorzano A, Sebastián D, Segalés J, Palacín M | title = The molecular machinery of mitochondrial fusion and fission: An opportunity for drug discovery? | journal = Current Opinion in Drug Discovery & Development | volume = 12 | issue = 5 | pages = 597–606 | date = September 2009 | pmid = 19736619 }} In obesity and type II diabetes, MFN2 expression has been found to be reduced.{{cite journal | vauthors = Bach D, Naon D, Pich S, Soriano FX, Vega N, Rieusset J, Laville M, Guillet C, Boirie Y, Wallberg-Henriksson H, Manco M, Calvani M, Castagneto M, Palacín M, Mingrone G, Zierath JR, Vidal H, Zorzano A | display-authors = 6 | title = Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6 | journal = Diabetes | volume = 54 | issue = 9 | pages = 2685–93 | date = September 2005 | pmid = 16123358 | doi = 10.2337/diabetes.54.9.2685 | doi-access = free }}{{cite journal | vauthors = Kipanyula MJ, Contreras L, Zampese E, Lazzari C, Wong AK, Pizzo P, Fasolato C, Pozzan T | display-authors = 6 | title = Ca2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2 | journal = Aging Cell | volume = 11 | issue = 5 | pages = 885–93 | date = October 2012 | doi = 10.1111/j.1474-9726.2012.00858.x | pmid = 22805202 | s2cid = 36750635 | doi-access = free | hdl = 10261/112103 | hdl-access = free }} In turn, MFN2 down-regulation activates JNK pathway, favouring the formation of lipid intermediates that lead to insulin resistance. Recent studies have also shown that mitochondria arrest fusion by down-regulating MFN2 in obesity and diabetes, which leads to a fragmented mitochondrial network. This fragmentation is obvious in the pancreatic beta-cells in the Islets of Langerhans and can inhibit mitochondrial quality control mechanisms such as mitophagy and autophagy - leading to a defect in insulin secretion and eventual beta-cell failure.{{cite journal | vauthors = Trudeau KM, Colby AH, Zeng J, Las G, Feng JH, Grinstaff MW, Shirihai OS | title = Lysosome acidification by photoactivated nanoparticles restores autophagy under lipotoxicity | journal = The Journal of Cell Biology | volume = 214 | issue = 1 | pages = 25–34 | date = July 2016 | pmid = 27377248 | pmc = 4932370 | doi = 10.1083/jcb.201511042 }} The expression of MFN2 in skeletal muscle is proportional to insulin sensitivity in this tissue,{{cite journal | vauthors = Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J, Daugaard JR, Lloberas J, Camps M, Zierath JR, Rabasa-Lhoret R, Wallberg-Henriksson H, Laville M, Palacín M, Vidal H, Rivera F, Brand M, Zorzano A | display-authors = 6 | title = Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 19 | pages = 17190–7 | date = May 2003 | pmid = 12598526 | doi = 10.1074/jbc.M212754200 | doi-access = free }} and its expression is reduced in high-fat diet fed mice{{cite journal | vauthors = Sorianello E, Soriano FX, Fernández-Pascual S, Sancho A, Naon D, Vila-Caballer M, González-Navarro H, Portugal J, Andrés V, Palacín M, Zorzano A | display-authors = 6 | title = The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells | journal = Cardiovascular Research | volume = 94 | issue = 1 | pages = 38–47 | date = April 2012 | pmid = 22253285 | doi = 10.1093/cvr/cvs006 | doi-access = free | hdl = 2445/60798 | hdl-access = free }} and Zucker fatty rats.

In heart, the embryonic combined MFN1/MFN2 deletion is lethal for mice embryo, while in adults it induces a progressive and lethal dilated cardiomyopathy.{{cite journal | vauthors = Chen Y, Liu Y, Dorn GW | title = Mitochondrial fusion is essential for organelle function and cardiac homeostasis | journal = Circulation Research | volume = 109 | issue = 12 | pages = 1327–31 | date = December 2011 | pmid = 22052916 | doi = 10.1161/circresaha.111.258723 | pmc = 3237902 }} A modest cardiac hypertrophy, associated to a tendency of MFN2-deprived mitochondria was observed caused by an increased resistance to Ca²⁺-mediated cell death stimuli.{{cite journal | vauthors = Papanicolaou KN, Khairallah RJ, Ngoh GA, Chikando A, Luptak I, O'Shea KM, Riley DD, Lugus JJ, Colucci WS, Lederer WJ, Stanley WC, Walsh K | display-authors = 6 | title = Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes | journal = Molecular and Cellular Biology | volume = 31 | issue = 6 | pages = 1309–28 | date = March 2011 | pmid = 21245373 | doi = 10.1128/mcb.00911-10 | pmc = 3067905 }} Furthermore, reduced expression of MFN2 and subsequent disruption of sarcoplasmic reticulum-mitochondrial contacts was observed to associate with atrial fibrillation in Drosophila.{{Cite journal |last=Li |first=Jin |last2=Qi |first2=Xi |last3=Ramos |first3=Kennedy S. |last4=Lanters |first4=Eva |last5=Keijer |first5=Jaap |last6=de Groot |first6=Natasja |last7=Brundel |first7=Bianca |last8=Zhang |first8=Deli |date=2022-10-04 |title=Disruption of Sarcoplasmic Reticulum-Mitochondrial Contacts Underlies Contractile Dysfunction in Experimental and Human Atrial Fibrillation: A Key Role of Mitofusin 2 |url=https://pubmed.ncbi.nlm.nih.gov/36172949/ |journal=Journal of the American Heart Association |volume=11 |issue=19 |pages=e024478 |doi=10.1161/JAHA.121.024478 |issn=2047-9980 |pmc=9673721 |pmid=36172949}} While it is undisputed the importance of MFN2 in cardiomyocytes physiology, clarification of whether its pro-fusion activity or other functionalities of the protein are involved will require further investigations.

Studying the mechanisms of mitochondrial function, more specifically MFN2 function, during tumorigenesis is critical for the next generation of cancer therapeutics. Recent studies have shown that dysregulation of the mitochondrial network can have an effect on MFN2 proteins, provoking mitochondrial hyperfusion and a multidrug resistant (MDR) phenotype in cancer cells.{{cite journal | vauthors = Vyas S, Zaganjor E, Haigis MC | title = Mitochondria and Cancer | journal = Cell | volume = 166 | issue = 3 | pages = 555–566 | date = July 2016 | pmid = 27471965 | doi = 10.1016/j.cell.2016.07.002 | pmc = 5036969 | url = }} MDR cancer cells have a much more aggressive behaviour and they are very invasive with a better ability to metastasize.{{cite book | vauthors = Brown JM | title = Oxygen Biology and Hypoxia | chapter = Tumor hypoxia in cancer therapy | series = Methods in Enzymology | volume = 435 | pages = 297–321 | date = 2007 | pmid = 17998060 | doi = 10.1016/s0076-6879(07)35015-5 | publisher = Elsevier | isbn = 978-0-12-373970-4 }} All these factors lead to a poor cancer prognosis and, therefore, novel therapeutic strategies for targeting and eradicating MDR TNBC cells are required. It has been hypothesized that mitochondrial hyperfusion is one of the main mechanisms that makes cells resistant to traditional chemotherapy treatments. Hence, inhibiting mitochondrial fusion would sensitize cancer cells to chemotherapy, making it a significantly more effective treatment. In order to inhibit mitochondrial hyperfusion, an anti-MFN2 peptide has to be used, in order to bind to the mitochondria membrane MFN2 proteins to prevent them from building the mitochondrial network.{{cite journal | vauthors = Milane L, Trivedi M, Singh A, Talekar M, Amiji M | title = Mitochondrial biology, targets, and drug delivery | journal = Journal of Controlled Release | volume = 207 | pages = 40–58 | date = June 2015 | pmid = 25841699 | doi = 10.1016/j.jconrel.2015.03.036 }} The aim of the anti-MFN2 peptide is to make MFN2 not functional so it cannot participate in mitochondrial fusion and in the operation of the mitochondrial network. In this way, hyperfusion will not occur and chemotherapy drugs would be much more successful. However, further investigations are required in this field as there are still lots of unknowns.

{{reflist}}

{{refbegin}}

• {{cite journal |vauthors=Pawlikowska P, Orzechowski A |title=[Role of transmembrane GTPases in mitochondrial morphology and activity] |journal=Postepy Biochem. |volume=53 |issue= 1 |pages= 53–9 |year= 2007 |pmid= 17718388 }}
• {{cite journal |vauthors=Zorzano A, Bach D, Pich S, Palacín M |title=[Role of novel mitochondrial proteins in energy balance] |journal=Revista de medicina de la Universidad de Navarra |volume=48 |issue= 2 |pages= 30–5 |year= 2004 |pmid= 15382611 }}

{{refend}}

• [https://www.ncbi.nlm.nih.gov/books/NBK1285/ GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 2]
• {{PDBe-KB2|O95140|Mitofusin-2}}