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. 2016 Dec 12;11(12):e0167908.
doi: 10.1371/journal.pone.0167908. eCollection 2016.

Voltage-Dependent Anion Channel 1(VDAC1) Participates the Apoptosis of the Mitochondrial Dysfunction in Desminopathy

Huanyin Li  1 , Lan Zheng  1 , Yanqing Mo  1 , Qi Gong  1 , Aihua Jiang  1 , Jing Zhao  1
Affiliations

Voltage-Dependent Anion Channel 1(VDAC1) Participates the Apoptosis of the Mitochondrial Dysfunction in Desminopathy

Huanyin Li et al. PLoS One. .

Abstract

Desminopathies caused by the mutation in the gene coding for desmin are genetically protein aggregation myopathies. Mitochondrial dysfunction is one of pathological changes in the desminopathies at the earliest stage. The molecular mechanisms of mitochondria dysfunction in desminopathies remain exclusive. VDAC1 regulates mitochondrial uptake across the outer membrane and mitochondrial outer membrane permeabilization (MOMP). Relationships between desminopathies and Voltage-dependent anion channel 1 (VDAC1) remain unclear. Here we successfully constructed the desminopathy rat model, evaluated with conventional stains, containing hematoxylin and eosin (HE), Gomori Trichrome (MGT), (PAS), red oil (ORO), NADH-TR, SDH staining and immunohistochemistry. Immunofluorescence results showed that VDAC1 was accumulated in the desmin highly stained area of muscle fibers of desminopathy patients or desminopathy rat model compared to the normal ones. Meanwhile apoptosis related proteins bax and ATF2 were involved in desminopathy patients and desminopathy rat model, but not bcl-2, bcl-xl or HK2.VDAC1 and desmin are closely relevant in the tissue splices of deminopathies patients and rats with desminopathy at protein lever. Moreover, apoptotic proteins are also involved in the desminopathies, like bax, ATF2, but not bcl-2, bcl-xl or HK2. This pathological analysis presents the correlation between VDAC1 and desmin, and apoptosis related proteins are correlated in the desminopathy. Furthermore, we provide a rat model of desminopathy for the investigation of desmin related myopathy.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. VDAC1 is involved in the desminopathy patients.
The skeletal muscle fibers of desminopathy patients were treated with HE, MGT, immunohistochemical, NADH, SDH or PAS stain (A); individual atypical RRF and individual lipid droplets by MGT and ORO stains were shown in (B); desmin in the muscle fibers of patients were detected by immunohistochemistry as shown in (C), the muscle fiber of normal person was set as a control (C); VDAC1 and desmin in the muscle fibers of desminopathy patients were analyzed by immunofluorescence as shown in (D). Scale bars, 50μm.
Fig 2
Fig 2. Apoptosis related proteins are involved in the desminopathy patients.
The apoptosis related proteins bax (A), bcl-2 (B), bcl-xl (C), ATF2 (D) and HK2 (E) of normal person (control) or desminopathy patients were detected by immunofluorescence; in the normal muscle fibers, bax was lightly stained in type 1 muscle fiber, and deeply stained in type 2 muscle fiber as shown in (A, right). Scale bars, 50μm.
Fig 3
Fig 3. VDAC1 is involved in the desminopathy rat model.
In the desminopathy rat model, normal (control) or mutant desmin(rAd5-DES) transferred muscle fibers were analyzed by immunohistochemistry (A); desminopathy muscle fibers were detected by HE, MGT, NSE, immunohistochemical, PAS, ORO, NADH or SDH stain (B); VDAC1 and desmin in the normal or desminopathy muscle fibers were detected by immunofluorescence as shown in (C). Scale bars, 50μm.
Fig 4
Fig 4. Apoptosis related proteins are involved in the deminopathy rat model.
Apoptosis related proteins bax (A), bcl-2 (B), bcl-xl (C), ATF2 (D) or HK2 (E) was analyzed by immunofluorescence in the normal (control) or desminopathy muscle fibers. Scale bars, 50μm.
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Grants and funding

This work was supported by Minhang District Natural Science Foundation Project in 2016 (2016MHZ20), ShangHai, China.