Can different expression of mitofusins be involved in pathomechanism of particular mitochondrial diseases?

• Autorzy: Kawalec M. , Neska J. , Kabzinska D. , Zablocka B.
• Języki publikacji: EN

Abstrakty

EN

Mitochondrial homeostasis, resulting from fusion and fission processes together with mitophagy and mitogenesis, are widely studied nowadays. This is probably because we know more and more about the role of mitochondria in metabolic diseases (diabetes, hypertension), neurodegeneration (Parkinson’s Disease, Alzheimer’s Disease), but also in broad spectrum of inherited neurological syndromes (CharcotMarie-Tooth). In our studies we aimed to examine the expression pattern of particular mitochondrial proteins, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), in mouse tissues. We aim to verify, whether potential differences in expression of those proteins can by implicated in pathomechanism of Charcot-Marie-Tooth type 2A neuromyopathy, related to mitofusion 2 gene mutations. Mitofusins are mitochondrial GTPases, implicated in fusion of outer mitochondrial membrane. In this process, mitofusins juxtapose two mitochondria by combining homo- and heterodimers at the surface of two outer mitochondrial membranes. Although there is 63% homology between mitofusins, it is proved, that they show some different functions. As Mfn1 KO present more severe aberrations in mitochondrial network formation than Mfn2 deficient cells, Mfn1 is considered to have stronger fusion activity. It is also suspected, that it is Mfn1 that links fusion of outer and inner mitochondrial membranes. Nevertheless, Mfn2, but not Mfn1, is present at endoplasmic reticulum (ER). Mfn2 tethers ER to mitochondria facilitating calcium flux and (indirectly) autophagy. Moreover, Mfn2 seems to have some regulatory effect on cell cycle, beyond its fusion activity and its lower expression seems to correlate with insulin resistance and hyper proliferation in hypertension. So, the question is, how much these two proteins can replace each other while playing so different roles? Moreover, it is suggested that CMT2A predominantly affects peripheral nerves because mutated, malfunctioned Mfn2 is insufficiently compensated by Mfn1 due to its low expression particularly in this type of tissue. To discuss this issue, we have investigated the expression of Mfn1 and Mfn2, as well as protein content, in tissues, performing Real Time PCR and Western Blot studies. Preliminary data from Western blot analysis displayed equally high relative level of both mitofusins in nervous system (dorsal root ganglia, cerebral cortex, cerebellum, spinal cord) in comparison to peripheral organs (muscle, heart, liver, kidney, skin). Moreover, Mfn1 expression seems significantly lower in dorsal root ganglia, which are well established model of peripheral nervous system. This phenomenon was not observed for other tissues, even from central nervous system. So it seems quite possible, that axonal damage of peripheral nerves in CMT2A, may be observed due to the poor compensation of dysfunctional Mfn2 by fully functional Mfn1, which is not expressed at sufficient level. The project was supported by NSC grant NN402474640

Słowa kluczowe

EN

mitofusin 1; mitofusin 2; pathomechanism; mitochondrial disease; mitochondrial homeostasis; metabolic disease; neurological syndrome; protein expression; gene mutation; mitochondrial membrane

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.188-189

Twórcy

autor

Kawalec M.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Neska J.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Kabzinska D.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Zablocka B.

• Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland