Table 2.1.

Local (organellar) versus global (cellular) controls of mitochondrial dynamics

Control mechanism	Outcome	References
Fission
Global cellular control
Recruitment of Drp1 to mitochondria is calcium dependent and regulated by calcineurin	Elevated cytosolic calcium levels activate calcineurin to dephosphorylate Drp1	Yoon et al. (2003), Kong et al. (2005), Kaddour-Djebbar et al. (2010), Hom et al. (2010), Cribbs and Strack (2007), Cereghetti et al. (2008, 2010), Tan et al. (2011), Wang et al. (2011c)
Prolonged exercise increases transcription and expression of Fis1 while decreasing mitofusins	Acute increases in metabolic demands of skeletal muscle stimulate fission	Ding et al. (2010b)
BH3 only proteins and Bax/Bak induce fission, Bax/Bak in healthy cells control fusion through MFN2	Interact at mitochondrial scission sites to promote fission	Karbowski (2010), Shroff et al. (2009), Karbowski et al. (2002), Wu et al. (2011), Sheridan et al. (2008)
Sumoylation of Drp1 occurs by multiple enzymes and is present at fission sites	Protects Drp1 from degradation and increases fission activity	Figueroa-Romero et al. (2009), Braschi et al. (2009), Harder et al. (2004), Dimmer and Scorrano (2006)
High levels of oxidative stress causes fragmentation of the mitochondrial network	Drp1 phosphorylation and Bid translocation increase fission activity	Grohm et al. (2010), Qi et al. (2011)
Amino acid and other nutrient deprivation causes hyperfusion by downregulation of Drp1	Fused mitochondrial network evades autophagic degradation during starvation	Rambold et al. (2011a, b)
Drp1 expression is transcriptionally activated by p53 protein in response to apoptotic stimuli	The miR-30 family of micro-RNA limit fission by suppressing p53 expression and Drp1 activation	Li et al. (2010)
Inhibition of histone deacetylases induces mitochondrial elongation	Fused networks occur due to decreased Fis1 expression and reduced Drp1 translocation	Lee et al. (2012)
Phosphorylation of Drp1 has opposing effects on fission depending on the kinase	Example: phosphorylation of Drp1 by cAMP kinase increases yet PKC delta decreases fission	Cribbs and Strack (2007), Qi et al. (2011), Kim et al. (2011)
Local organelle control
Knockdown of Mff promotes elongation of the network and overexpression of Mff promotes fission	Mff recruits Drp-1 to fission sites on the outer membrane independently of hFis1	Otera et al. (2010), Gandre-Babbe and van der Bliek (2008)
Blocking the mitochondrial Na⁺/Ca²⁺ exchanger increases interaction between Drp1 and Fis1	Elevated levels of mitochondrial calcium increases fission activity	Kaddour-Djebbar et al. (2010)
Treatment with cysteine-alkylators inhibits fission and fast mitochondrial movement	Loss of movement coincided with microtubule- dependent thin mitochondrial extensions	Bowes and Gupta (2005, 2008)
Conformation specificities and self-interaction dictate the ability of Fis1 to recruit fission machinery	Fis1 activity is regulated by two interaction interfaces and its ability to oligomerize	Serasinghe and Yoon (2008), Zhang and Chan (2007)
Fusion
Global cellular control
Activation of PGC1a/PGC-1b/ERRa induces MFN2 mRNA. PGC-1b induces mitochondrial fusion by Mfn2	Increased fusion activity accompanies mitochondrial biogenesis	Liesa et al. (2008), Soriano et al. (2006)
Mitochondrial tubularization and network fusion at G1-S of cell cycle	G1-S stimulates global mitochondrial fusion, mitosis stimulates fission	Lee et al. (2004), Taguchi et al. (2007), Arakaki et al. (2006), Kashatus et al. (2011)
Variation in isoform expression of OPA1 occurs via alternative gene splicing	Expression of the eight splice variants differs across tissues and alter fusion and apoptotic activity	Song et al. (2007), Olichon et al. (2007), Frezza et al. (2006)
The promoter region of MFN2 is a target of the tumor suppressor protein, p53	Mfn2 mRNA and protein levels are up-regulated in a p53-dependant manner	Wang et al. (2010)
Local organelle control
Functional interaction of OPA1 with MFN1 and physical interaction between mitofusins and OPA1	Protein complex spans the two mitochondrial membranes and permits fusion activity	Cipolat et al. (2004), Guillery et al. (2008)
OPA1 processing by metalloproteases can block fusion activity and alter cristae structure	Provides a mechanism for fusion inhibition at the local level by protease activity	Song et al. (2007, 2009), Ehses et al. (2009), Duvezin-Caubet et al. (2006), Griparic et al. (2007), Guillery et al. (2008), Baricault et al. (2007), Kieper et al. (2010)
Low levels of local GTP induce outer membrane tethering while complete fusion events require high intra-mitochondrial GTP levels	Initial fusion is promoted in energy deficient environments yet complete fusion is regulated by energetic status of the organelles	Meeusen et al. (2006)
G-protein beta2 is enriched in the mitochondrial membrane and interacts with Mfn1 to regulate fusion	Gbeta2 regulates the mobility of Mfn1 within the outer membrane and promotes fusion	Zhang et al. (2010)
Bcl-x(L) increases rates of fusion and fission with an observed overall network elongation	Bcl-x(L) increases mitochondrial mass concurrent with elevated dynamics cycling	Berman et al. (2009)
Solitary period
Global cellular control
Global ADP levels increase mitochondrial movement to synapses	ADP signals mitochondrial motility	Mironov (2009)
G-protein coupled receptor, Ga12, is expressed in mitochondria and regulates motility	GPCRs are sensitive to GDP/GTP levels and can regulate mitochondrial motility	Andreeva et al. (2008)
Bnip3 expression induces Drp1 mediated fission and parkin translocation in adult myocytes	Increased fission activity and parkin translocation enhanced mitophagy	Lee et al. (2011a)
Local organelle control
Mitochondrial movement along microtubules occurs in an energy-dependent manner	Individual mitochondria move at different rates along microtubules based on ATP levels	Yi et al. (2004), Miller and Sheetz (2004), Guo et al. (2005)
Local redox status of mitochondria impacts membrane potential and velocity of movement	Elevated oxidation leads to depolarization and to increased motility	Gerencser and Nicholls (2008)
PINK1 and Parkin target Miro, mitofusins and other outer membrane proteins for proteasomal degradation and promote mitophagy	Proteasomal degradation of Miro and mitofusins isolate and immobilize mitochondria which increases the pre-autophagic pool	Tanaka et al. (2010a), Wang et al. (2011b), Weihofen et al. (2009), Ziviani et al. (2010), Ziviani and Whitworth (2010), Poole et al. (2008, 2010), Yang et al. (2008), Glauser et al. (2011), Rakovic et al. (2011), Gegg et al. (2010)