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Hsp90 involved in mitochondrial quality control through mitophagy and fusion/fission pathways

Thursday, September 13, 2018 — Poster Session IV

3:30 p.m. – 5:00 p.m.
FAES Terrace
NIDDK
CELLBIO-9

Authors

  • CP LIN
  • DC MASISON

Abstract

Mitochondria are highly dynamic organelles that undergo fusion, fission, and regulated degradation continuously. These regulatory processes play critical roles in maintaining the quantity as well as quality of the mitochondrial population. A genetic screen revealed that Hsp90 cooperates with Mrp10, Mtf2, Atp5, Atg20 and Irs4 involved in mitochondrial homeostasis through mitophagy pathway. Hsp90 is also involved in mitochondrial integrity by fusion and fission pathway. atg20Δ combined with hsp90 middle domain mutant not only showed severe mitochondrial fragmented morphology, but also defect in mitochondrial functionality reflected by decline in ATP production and membrane potential. This fragmented phenotype is attributed to the elevated expression of Drp1, the key protein for mitochondrial fission. By rebalance the dosage of fusion and fission, the network phenotype is restored. Increasing the dosage of Ugo1, a molecule involved in mitochondrial outer membrane fusion, recover the phenotype morphologically. Moreover, expressing Mdv1, Caf4 and Mdm36, molecules served as Drp1 adaptors, also bring the normal network morphology back. Upon nitrogen starvation, a dramatic accumulation of lipid droplets (LDs) was observed, which was correlated with a decline in cell survival frequency due to blocked of fatty acid uptake by mitochondria. We conclude that Hsp90 is involved in mitochondrial homeostasis in three aspects: through mitophagy, fusion/fission, and lipid metabolism.

Category: Cell Biology