Mechanism of Arachidonic Acid Accumulation during Aging in Mortierella alpina: A Large-Scale Label-Free Comparative Proteomics Study

J Agric Food Chem. 2016 Nov 30;64(47):9124-9134. doi: 10.1021/acs.jafc.6b03284. Epub 2016 Nov 16.

Abstract

Arachidonic acid (ARA) is an important polyunsaturated fatty acid having various beneficial physiological effects on the human body. The aging of Mortierella alpina has long been known to significantly improve ARA yield, but the exact mechanism is still elusive. Herein, multiple approaches including large-scale label-free comparative proteomics were employed to systematically investigate the mechanism mentioned above. Upon ultrastructural observation, abnormal mitochondria were found to aggregate around shrunken lipid droplets. Proteomics analysis revealed a total of 171 proteins with significant alterations of expression during aging. Pathway analysis suggested that reactive oxygen species (ROS) were accumulated and stimulated the activation of the malate/pyruvate cycle and isocitrate dehydrogenase, which might provide additional NADPH for ARA synthesis. EC 4.2.1.17-hydratase might be a key player in ARA accumulation during aging. These findings provide a valuable resource for efforts to further improve the ARA content in the oil produced by aging M. alpina.

Keywords: Mortierella alpina; aging; arachidonic acid; molecular mechanism; proteomics.

Publication types

  • Comparative Study

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Arachidonic Acid / metabolism*
  • Cluster Analysis
  • Culture Media
  • Delta-5 Fatty Acid Desaturase
  • Down-Regulation
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal*
  • Gene Ontology
  • Isocitrate Dehydrogenase / metabolism
  • Ketone Oxidoreductases / metabolism
  • Linoleoyl-CoA Desaturase / genetics
  • Linoleoyl-CoA Desaturase / metabolism
  • Malate Dehydrogenase / metabolism
  • Mortierella / genetics
  • Mortierella / metabolism*
  • Proteomics*
  • Reactive Oxygen Species / metabolism
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Up-Regulation

Substances

  • Culture Media
  • Delta-5 Fatty Acid Desaturase
  • Fungal Proteins
  • Reactive Oxygen Species
  • Arachidonic Acid
  • Malate Dehydrogenase
  • Isocitrate Dehydrogenase
  • Fatty Acid Desaturases
  • Stearoyl-CoA Desaturase
  • Linoleoyl-CoA Desaturase
  • delta-12 fatty acid desaturase
  • Ketone Oxidoreductases
  • pyruvate dehydrogenase (NADP+)
  • Acetyl-CoA Carboxylase