However, it may be mediated by mitochondrial hyperfusion leading to aberrant cyclin E expression during G2 and replication stress that induces the G2/M checkpoint.
Together, these results indicate that endogenous Trak1 is required for stress-induced mitochondrial hyperfusion.
Furthermore, Trak1 is required for stress-induced mitochondrial hyperfusion and pro-survival response.
Conversely, increasing Trak1 protein level in cells causes a mitochondrial hyperfusion phenotype with elongated and enlarged mitochondria.
Our work reveals that Trak1 participates in stress-induced mitochondrial hyperfusion and promotes cell survival under stress conditions.
Open image in new window Figure 4 Trak1 overexpression induces mitochondrial hyperfusion and this effect is reduced by hypertonia-linked Trak1 mutation.
Open image in new window Open image in new window Figure 10 Stress-induced mitochondrial hyperfusion and pro-survival response require Trak1.
Although the molecular mechanism underlying stress-induced mitochondrial hyperfusion is poorly understood, recent evidence indicates that this mitochondrial hyperfusion process requires Mfn1, OPA1, and OPA1-regulating protein SLP-2, but not Mfn2 or Mfn2-regulating proteins Bax and Bak (Gomes et al., 2011; Rambold et al., 2011; Tondera et al., 2009).
In this study, we identified a novel function for Trak1 in regulation of mitochondrial fusion and showed that Trak1 is required for stress-induced mitochondrial hyperfusion and pro-survival response.
Our finding that depletion of Trak1 not only abolishes the ability of mitochondria to hyperfuse but also reduces cell survival under stress conditions reveals an essential role of Trak1 in mediating stress-induced mitochondrial hyperfusion and pro-survival response.
