Mitochondrial dysfunction in amyotrophic lateral sclerosis

Ping Shi, Jozsef Gal, David M. Kwinter, Xiaoyan Liu, Haining Zhu

Research output: Contribution to journalReview articlepeer-review

170 Scopus citations


The etiology of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains to be better understood. Based on the studies from ALS patients and transgenic animal models, it is believed that ALS is likely to be a multifactorial and multisystem disease. Many mechanisms have been postulated to be involved in the pathology of ALS, such as oxidative stress, glutamate excitotoxicity, mitochondrial damage, defective axonal transport, glia cell pathology and aberrant RNA metabolism. Mitochondria, which play crucial roles in excitotoxicity, apoptosis and cell survival, have shown to be an early target in ALS pathogenesis and contribute to the disease progression. Morphological and functional defects in mitochondria were found in both human patients and ALS mice overexpressing mutant SOD1. Mutant SOD1 was found to be preferentially associated with mitochondria and subsequently impair mitochondrial function. Recent studies suggest that axonal transport of mitochondria along microtubules and mitochondrial dynamics may also be disrupted in ALS. These results also illustrate the critical importance of maintaining proper mitochondrial function in axons and neuromuscular junctions, supporting the emerging "dying-back" axonopathy model of ALS. In this review, we will discuss how mitochondrial dysfunction has been linked to the ALS variants of SOD1 and the mechanisms by which mitochondrial damage contributes to the disease etiology.

Original languageEnglish
Pages (from-to)45-51
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number1
StatePublished - Jan 2010

Bibliographical note

Funding Information:
The authors' research was in part supported by the NIH grants R01NS049126 and R21AG032567 to H.Z . The support from NIH/NCRR Center of Biomedical Research Excellence in the Molecular Basis of Human Disease (COBRE, P20RR020171 ) is acknowledged.


  • Amyotrophic lateral sclerosis
  • Axonal transport
  • Mitochondrial dynamics
  • Mitochondrial function
  • Mutant SOD1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


Dive into the research topics of 'Mitochondrial dysfunction in amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this