Keratins modulate the shape and function of hepatocyte mitochondria: a mechanism for protection from apoptosis

GZ Tao, KS Looi, Diana Toivola, P Strnad, Q Zhou, J Liao, YQ Wei, A Habtezion, MB Omary

Research output: Contribution to journalReview Article or Literature Reviewpeer-review

52 Citations (Scopus)

Abstract

Absence or mutation of keratins 8 (K8) or 18 (K18) cause predisposition to liver injury and apoptosis. We assessed the mechanisms of hepatocyte keratin-mediated cytoprotection by comparing the protein expression profiles of livers from wildtype and K8-null mice using two-dimensional differential-ingel-electrophoresis (2D-DIGE) and mass spectrometry. Prominent among the alterations were those of mitochondrial proteins, which were confirmed using 2D-DIGE of purified mitochondria. Ultrastructural analysis showed that mitochondria of livers that lack or have disrupted keratins are significantly smaller than mitochondria of wild-type livers. Immunofluorescence staining showed irregular distribution of mitochondria in keratin-absent or keratin-mutant livers. K8-null livers have decreased ATP content; and K8-null mitochondria have less cytochrome c, increased release of cytochrome c after exposure to Ca2+ and oxidative stimulation, and a higher sensitivity to Ca2+-induced permeability transition. Therefore, keratins play a direct or indirect role in regulating the shape and function of mitochondria. The effects of keratin mutation on mitochondria are likely to contribute to hepatocyte predisposition to apoptosis and oxidative injury, and to play a pathogenic role in keratin-mutation-related human liver disease.
Original languageUndefined/Unknown
Pages (from-to)3851–3855
Number of pages5
JournalJournal of Cell Science
Volume122
DOIs
Publication statusPublished - 2009
MoE publication typeA2 Review article in a scientific journal

Keywords

  • Keratin 8
  • Keratin 18
  • Cytoprotection
  • Cytochrome c release
  • Mitochondria
  • intermediate filaments
  • liver injury

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