Mitochondrial dynamics and inherited peripheral nerve diseases

Davide Pareyson, Paola Saveri, Anna Sagnelli, Giuseppe Piscosquito

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2 mutations cause CMT type 2A by altering mitochondrial fusion and trafficking along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT type which in most cases is characterized by early onset and rather severe course. GDAP1 mutations also alter fission, fusion and transport of mitochondria and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR-CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its heterozygous mutations lead to early-onset and progressive dominant optic atrophy which may be complicated by other neurological symptoms including peripheral neuropathy. Mutations in several proteins fundamental for the axonal transport or forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT, distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed, mitochondrial transport involves directly or indirectly components of the kinesin superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2), implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such as heat shock proteins (HSPs) also have a fundamental role in mitochondrial transport and mutations in some of related encoding genes cause peripheral neuropathy (TUBB3, NEFL, HSPB1, HSPB8, HSPB3, DNAJB2). In this review, we address the abnormalities in mitochondrial dynamics and their role in determining CMT disease and related neuropathies.

Original languageEnglish
Pages (from-to)66-77
Number of pages12
JournalNeuroscience Letters
Volume596
DOIs
Publication statusPublished - Jun 2 2015

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Mitochondrial Dynamics
Charcot-Marie-Tooth Disease
Peripheral Nervous System Diseases
Mutation
Autosomal Dominant Optic Atrophy
Mitochondria
Axonal Transport
Microtubules
Dynamin II
Hereditary Sensory and Autonomic Neuropathies
Hereditary Spastic Paraplegia
Dyneins
Kinesin
Proteins
Intermediate Filaments
Mitochondrial Membranes
Heat-Shock Proteins
Cytoskeleton
Peripheral Nerves
Axons

Keywords

  • Axonal transport
  • Charcot-Marie-Tooth disease
  • GDAP1
  • MFN2
  • Mitochondrial dynamic
  • Mitochondrial fusion and fission

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Mitochondrial dynamics and inherited peripheral nerve diseases. / Pareyson, Davide; Saveri, Paola; Sagnelli, Anna; Piscosquito, Giuseppe.

In: Neuroscience Letters, Vol. 596, 02.06.2015, p. 66-77.

Research output: Contribution to journalArticle

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