Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: Ultrastructural and immunohistochemical studies

Shiro Matsubara, Kota Bokuda, Yuri Asano, Ryo Morishima, Keizo Sugaya, Kazuhito Miyamoto, Reiji Koide, Takashi Komori, Shigeaki Suzuki, Ichizo Nishino

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies occurs in patients both with and without history of statin-intake. The mechanisms of muscle fiber degeneration in this condition remain unknown. We studied pathological changes in muscle biopsies from three patients lacking history of statin-intake. Ultrastructural observations showed accumulation of degenerating mitochondria, glycogen granules and autophagic vacuoles, forming large composites in three cases, along with various nonspecific changes. The autophagic vacuoles often contained remnants of mitochondria, indicating mitophagy. Furthermore, upregulation of B-cell lymphoma 2/adenovirus E1B 19 kD-interacting protein 3 (BNIP3), a protein involved in mitophagy, was observed in two cases examined. In three cases of sporadic inclusion body myositis, two polymyositis, and three IMNM with anti-signal recognition particle antibody, BNIP3 was upregulated less frequently, and ultrastructural change of mitophagy was rarely seen. These findings suggested that mitophagy plays an important role in muscle fiber degeneration in IMNM with anti-HMGCR autoantibodies.

Original languageEnglish
JournalNeuromuscular Disorders
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Mitochondrial Degradation
Muscular Diseases
Autoantibodies
Oxidoreductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Vacuoles
Muscles
Mitochondria
Signal Recognition Particle
Inclusion Body Myositis
Polymyositis
B-Cell Lymphoma
Glycogen
Adenoviridae
Proteins
Up-Regulation
Biopsy
3-hydroxy-3-methylglutaryl-coenzyme A
Antibodies

Keywords

  • Autoantibody
  • BNIP3
  • HMGCR
  • Mitophagy
  • Necrotizing myopathy
  • Programmed cell death

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

Cite this

Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies : Ultrastructural and immunohistochemical studies. / Matsubara, Shiro; Bokuda, Kota; Asano, Yuri; Morishima, Ryo; Sugaya, Keizo; Miyamoto, Kazuhito; Koide, Reiji; Komori, Takashi; Suzuki, Shigeaki; Nishino, Ichizo.

In: Neuromuscular Disorders, 01.01.2018.

Research output: Contribution to journalArticle

Matsubara, Shiro ; Bokuda, Kota ; Asano, Yuri ; Morishima, Ryo ; Sugaya, Keizo ; Miyamoto, Kazuhito ; Koide, Reiji ; Komori, Takashi ; Suzuki, Shigeaki ; Nishino, Ichizo. / Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies : Ultrastructural and immunohistochemical studies. In: Neuromuscular Disorders. 2018.
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