An alternative model assumes a change in the conformational equilibrium by internally accumulating substrate.
Using transmission electron microscopy (TEM), we confirmed that there was indeed an increase in the number of autophagosomes/autolysosomes with accumulated substrates in the lumen (Fig. 4G).
This was not accompanied by significant reductions in the accumulated substrates, GC and GS.
Therapeutic approaches for SD have been investigated, including substrate reduction therapy [28], [29], bone marrow transplantation [30], [31], stem cell therapy [32] and enzyme replacement therapy [33], in which the aim is to reduce the accumulated substrates.
This can be achieved through rescue experiments by simultaneous deletion of the accumulated substrates, one at a time or in combination of a few if necessary.
Non-production surfaces that encounter beer and/or waste streams, such as floors, sinks, and grain-handling equipment, are typically only cleaned by hose and may accumulate substrates for supporting microbial growth and survival.
The accumulated substrates, in visceral cell types, cause the lysosomes to become distended, giving them a foamy appearance and the process ultimately ends in organ failure, similar to full blown classic lipid storage disorders [ 3, 13, 25].
Figure 3 summarizes the available KO models of cullin family members with a brief description of the KO phenotype and accumulated substrates, which likely contribute to the exhibited phenotypes.
Using ASP+-guided flow cytometry, we demonstrated that residual 2A amino acids attached to the C-terminus of the transcribed hNET markedly reduced the protein capacity to accumulate substrate into the cell.
