Mitochonria as antenna regulators

Hyun-Shik Lee

School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, South Korea

Cilia are antennas capable of sensing the environment. In the last few years, scientists have discovered that the single cilium on each cell receives and reconfigures the signals that form neurons, sculpt the body plan and organize the brain. In adults, cilia are required to heal wounds and grow cells, and when they malfunction, they can help cause cancer. Damage to primary cilia is now also linked to kidney disease, obesity and even the failure of adult neuron development.

Ciliogenesis begins as the duplication of centriole within the cytoplasm and each basal body migrate apical surface of multiciliated cell, where they dock to plasma membrane of apical surface. Finally, small vesicle trafficking convey ciliary components to docked basal body that assembly a ciliary axoneme and ciliary elongation. The vertebrate planar cell polarity (PCP) signaling pathway has previously been found to control polarized cell behaviors rather than cell fate.

We investigate that disruption of two genes have different functions (peroxiredoxin5: antioxidant enzyme, phosphoglycerate mutase 5: metabolic enzyme), affect vertebrate ciliogenesis. They regulate not only PCP-dependent convergent extension but also elicits embryonic phenotypes consistent with defective Hedgehog signaling. These defects in Hedgehog signaling resulted from a broad requirement for them in ciliogenesis. We show that these proteins govern apical tubulin assembly and control the orientation of ciliary microtubules. Moreover, accumulation of them underneath the basal apparatus of cilia (mitochondria) suggests that they may regulate ciliogenesis through a conserved PCP signaling pathway. Furthermore, loss of their expression induces bubbling of mitochondrial outer membranes and causes sequential disruption of mitochondrial membrane potentials through the generation of excess reactive oxygen species Moreover, ATP-driven elongation of cilia was also failes in ciliated cells. Finally, we also confirmed the phenotypes of loss of them in trachea of knock-out mice. Taken together, these data demonstrate that they are novel positive regulators for cilia formation during vertebrate development.