claim that Mfn2
overexpression reduces the expression of MICU1 and MICU2 to trigger influx of [Ca.sup.2+] into mitochondria , revealing the close relationship of mitochondrial dynamics with [Ca.sup.2+] homeostasis.
Mitochondrial fusion involves fusion of both the outer mitochondrial membrane and inner mitochondrial membrane, a process depending on mitofusin-1 (Mfn1), mitofusin-2 (Mfn2
), and OPA1 (a dynamin-related protein with GTPase activity) .
Mfn1 and Mfn2
antibodies were purchased from Santa Cruz Biotech, and OPA-1 antibody was purchased from BD Transduction Laboratories.
Antibodyto mitofusin-1 (Mfn1, 1: 1,000, rabbit), mitofusin-2 (Mfn2
, 1: 500, mouse), uncoupling protein 3 (UCP3, 1:500, rabbit), and voltage dependent anion channel 1 (VDAC1, 1: 1,000, rabbit) were from Abcam (Cambridge, UK).
Antibodies for PGC-1[alpha] (1: 1000), Mfn-1 (1: 500), Mfn2
(1:200), OPA-1 (1:500), metalloendopeptidase 1 (OMA1) (1:200), FIS1 (1:200), actin (1:200), and UCP-2 (1:500) were supplied by Santa Cruz Biotechnology (Santa Cruz, Ca, USA); anti-nuclear respiratory factor 1 (NRF1) (1 : 1000) and anti-mitochondrial transcription factor A (Tfam) (1: 1000) antibodies were obtained from Cell Signalling (Danvers, MA, USA); antibodies against UCP-3 (1: 500), Mn-super oxide dismutase (Mn-SOD) (1: 1000) and cytochrome c oxidase subunit 4 (COX-IV) (1: 1000) were from Millipore (Billerica, MA, USA).
Supporting this idea, it has been found that Mfn2
interacts with other Mfn2
molecules or with Drp1 through different regions in the Mfn2
protein to regulate fusion/fission balance .
Mitofusins 1 and 2 (Mfn1 and Mfn2
) and optic atrophy 1 (Opa1) induce mitochondrial fusion in the outer and inner mitochondrial membranes, respectively [88, 89], while dynamin-related protein 1 (Drp1) is a cytoplasmic protein that assembles into rings surrounding the mitochondrial outer membrane, where it interacts with fission protein 1 (Fis1) to promote fission [90, 91].
In animal models, mitofusin 2 (Mfn2
) plays a key role in mitochondrial muscle damage control, since in the aging process there is a progressive Mfn2
reduction in the skeletal muscle of the mice, besides, the Mfn2
ablation produces a gene mark of aging.
The study focused on two related proteins, MFN2
and MFN1, found on the outer membranes of mitochondria, structures inside the body's cells that act as powerhouses by converting food into energy.
Nevertheless, the data did not reveal a heterozygous or homozygous mutation in any of the exons of the CMT (GJB1, MFN2
, MPZ, TNF, GDAP1, etc.) or progressive myoclonic epilepsy ( PME ) (CSTB, KCNT1, ASAH1, GOSR2, etc.) genes.
PMP22, MPZ, MFN2
, GDAP1, NEFL, CX32, MYH14, LMNA, TRPV4, LITAF.
Despite this, the vast majority of cases are attributed to mutations in just four of these genes: PMP22, MPZ, GJB1, and MFN2
. CMT types 1 and 2 represent by far the largest proportion of patients; these classifications are based off features of demyelinating (CMT1) or axonal (CMT2) dysfunction.