This process leads to the rapid degradation of the TIM protein, allowing organisms to entrain at dawn to environmental cycles.

Tim9 and Tim10 make up the group of essential small Tim proteins that assist in transport of hydrophobic precursors across the intermembrane space.

Small Tim proteins are synthesised lacking a cleavable presequence, but instead containing internal targeting information and need to be imported to the intermembrane space.

Small Tim proteins are then maintained in active conformation within the intermembrane space by Hot13 (helper of Tims).

It is possible that Hot13 may have reducing effects on small Tim proteins as they counterbalance the harmful effects that oxidative agents exhibit.

Following import, beta barrel proteins are transpoted to the SAM complex by chaperone complexes, formed by assembly of the small Tim proteins.

This protein interacts with Mia40 during the import of intermembrane space proteins including the small Tim proteins Cox17 and Cox19 both of which have disulfide bonds.

Timeless- The tim gene encodes for the TIM protein that is critical in circadian regulation in Drosophila.

Furthermore, these mutant flies express low levels of PER and TIM proteins, indicating that Clock functions as a positive element in the circadian loop.

In light-dark cycles, TIM protein level decreases rapidly in late night/early morning, followed by the similar but more gradual changes in PER protein level.

In fact, these mutants expressed even higher cytosolic levels of PER than cells in which PER protein was associated with TIM protein.

The oscillations in the PER and TIM proteins presence causes oscillations in the their own and other genes' expression, which is the basis for circadian rhythmicity.

The exact role of TIM in mammals is still unclear, as Tim transcription does not oscillate rhythmically and the TIM protein remains in the nucleus.

The Jrk homozygotes expressed low, non-cycling levels of per and tim mRNA as well as PER and TIM protein.

Western blot analysis shows that homozygous cycle mutants have very little PER and TIM protein as well as low per and tim mRNA levels.

Researchers in Rosbash's lab also showed that tim mRNA levels and TIM protein levels have circadian rhythms that are similar to those of the period(per) and its product.

PER and TIM proteins then accumulate in the cytoplasm, translocate into the nucleus at night, and turn off their own transcription, thereby setting up a 24-hour oscillation of transcription and translation.

Young observed that without functional DBT protein, flies accumulated high levels of PER and these PER proteins would not disintegrate in the absence of pairing with TIM protein.

A point mutation in cry, which is required for flavin association in CRY protein, results in no PER or TIM protein cycling in either DD or LD.

The mammalian TIM protein levels do not shift with light signals, but there is reported interaction with the mammalian period protein PER1 and mammalian cryptochrome (CRY1 and CRY2).

Young's team suspected that the delay between the rise in mRNA levels of per and tim and the rise of PER and TIM protein were due to the effects of another protein.

After PER and TIM proteins accumulate in the cytoplasm and bind together, the PER-TIM complex translocates to the nucleus and interferes with the CYC-CLK protein complex function to inhibit its activation of transcription.