Fission and selective fusion govern mitochondrial segregation and elimination by autophagy (EMBO J, 2008, 27:433-446)

報告日期: 2008/06/03
報告時間: 16:05/16:55
報告學生: 許觀達
講評老師: 郭余民
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/970603-2.pdf

Fission and selective fusion govern mitochondrial segregation and elimination by autophagy

Twig et al., EMBO J. 2008; 27: 433-46.

 

Speaker: Guan-Da Syu 

Commentator: Dr. Yu-Min Kuo

Time: 2008/06/03, 16:05-16:55

Place: Room 602

 

Abstract:

Mitochondrial fusion and fission has been associated with mitochondrial membrane potential, mitochondrial respiratory activity and many cellular functions (ref 1).  In b-cells, accumulation of depolarized mitochondrial has been implicated with oxidative damage and impaired insulin secretion (ref 2&3).  The detail mechanisms of how fusion and fission events controlling the fate of mitochondria are still unclear.  The author tracked the photolabeled mitochondria (ref 4) and found out that mitochondrial frequently went fusion and fission cycles in a kiss and run pattern.  Fission generated uneven daughter, one exhibit high membrane potential while the other was depolarized and had a reduced fusion probability.  Moreover the fusion protein OPA1 level was decreased in depolarized mitochondria and lost its fusion ability.  The subpopulation of depolarized and solitary for a few hours, the mitochondrion would be removed autophagy.  Inhibition of the fission machinery by dominant negative DRP1 (DRP1K38A) or FIS1 RNAi decreased mitochondrial autophagy, more oxidized protein, reduced respiration and impaired insulin secretion.  Over-expression of OPA1 decreases mitochondrial autophagy.  Together, these findings suggest that fission followed by selective fusion segregates dysfunctional mitochondria and permits their removal by autophagy.

 

Reference:

1.     Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280: 26185–26192

2.     Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307: 384–387

3.     Maechler P, Jornot L, Wollheim CB (1999) Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic beta cells. J Biol Chem 274: 27905–27913

4.     Twig G, Graf SA, Wikstrom JD, Mohamed H, Haigh SE, Elorza A, Deutsch M, Zurgil N, Reynolds N, Shirihai OS (2006) Tagging and tracking individual networks within a complex mitochondrial web with photoactivatable GFP. Am J Physiol Cell Physiol 291: C176–C184