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Overview of mechanisms underlying the main mitochondrial peripheral neuropathies. (A) MFN2 is located in the outer mitochondrial membrane and
interacts with Miro and Milton proteins, which belong to the molecular complex that links mitochondria to kinesin (KHC) motors. (B) MFN2 participates in
bringing the outer membranes of two mitochondria into close proximity. Thus, MFN2 mutations can lead to defects in mitochondrial motility along the
cytoskeletal microtubular tracks, and to dysfunction in fusion of the outer mitochondrial membranes of opposing mitochondria. Similarly, mutations in
OPA1, which is located in the inner mitochondrial membrane, lead to dysfunction in the fusion process of the inner mitochondrial membrane. (C) Loss-offunction mutations in GDAP1, located in the outer mitochondrial membrane, can lead to dysfunction in the mitochondrial fission process, since GDAP1
Source: Mitochondrial Disorders, Neuromuscular Disorders, 2e
might be a positive effector of assembly of the fission mediator DRP1. Dysfunction is shown by red oblique bars. (D) Dysfunctions in the respiratory chain
Citation:
Amato Direct
AA, Russell
JA. Neuromuscular
2e; 2015
Available
at: http://mhmedical.com/
May
2017
can be due to
the following:
mutations
in mitochondrialDisorders,
protein-coding
genes
(red segment
of circular mtDNA)Accessed:
ND1, ND4,
and15,
ND6,
which encode
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2017
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for subunits of complex I (NADH dehydrogenase), and MTATP6, which encodes for a subunit of complex V (ATP-synthase); mutations in mitochondrial
tRNA-coding genes (light blue segment) MTTL1 and MTTK, which lead to dysfunction in transcription of mitochondrial protein-coding genes; or direct
mutations in the nuclear gene SURF1 (in green), which encodes an ancillary protein involved in complex IV (cytochrome c oxidase) assembly. Dysfunction