Contents

📒 Benard 2007

Mitochondrial bioenergetics and structural network organization1

Sciwheel

Introduction

Close relationship between energy production and mt-network organization.

  • Observations of Hackenbrock (Hackenbrock, 1966; Hackenbrock, 1968; Hackenbrock et al., 1971) revealed a rapid and reversible change of the mitochondrion from the so-called orthodox' to condensed' conformations upon activation of ATP synthesis

  • The opposite is also true, because pathological mutations in genes responsible for mitochondrial fusion or fission have been associated with alterations in the organization of the mt-network and with the inhibition of energy metabolism

Study: Analysis of the crosstalk between mitochondrial bioenergetics and organelle-network organization.

Results

DRP1 (fission) is inhibited by DRP1-targeting siRNA

https://user-images.githubusercontent.com/40054455/97544999-53526700-1a05-11eb-81ec-8ce82f75c344.png
(A) wild-type HeLa cells, and (B) non-induced and (C) induced HeLa cells

  • HeLa cells containing siRNA targeting DRP1 showed a slower rate of proliferation in glucose medium
  • Mitochondrial energy production is impaired in HeLa cells lacking DRP1
    • Isolated mitochondria from HeLa cells lacking DRP1 presented with a slower rate of state-4 and state-3 respirations

https://user-images.githubusercontent.com/40054455/97544943-40d82d80-1a05-11eb-960e-430eb654dd70.png
Mitochondrial energetics is altered in HeLa cells where DRP1 levels were decreased

https://user-images.githubusercontent.com/40054455/97544848-230ac880-1a05-11eb-8ccb-7b30d9fa0495.png
Mitochondrial membrane fluidity is increased

Discussion

https://user-images.githubusercontent.com/40054455/97545368-dd023480-1a05-11eb-92f5-ca8f9efb8e89.png
Mitochondrial flux-force-structure diagram

  • (b,c): OXPHOS uncoupling with CCCP
  • (d-f): respiratory chain inhibition with rotenone
  • (g,h): inhibition of mitochondrial ATP synthesis with oligomycin

Fragmentation by

  • The presence of uncouplers such as CCCP, DNP or FCCP
  • ρ0 cells
  • oligomycin, a specific inhibitor of the F1F0-ATP synthase
  • Hydroxycinamic acid, an inhibitor of the phosphate carrier
  • cyclosporine A, an inhibitor of the mPTP
  • Inhibition of respiratory chain complex I and complex III

Conclusion

The relationship between mitochondrial form and function are bidirectional


  1. Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, et al. Mitochondrial bioenergetics and structural network organization. J Cell Sci. 2007 Mar 1;120(Pt 5):838–48. ↩︎