Effects of acidosis on the structure, composition, and function of adult murine femurs.

Physiologic pH is maintained in a narrow range through multiple systemic buffering systems. Metabolic Acidosis (MA) is an acid-base disorder clinically characterized by a decrease in systemic pH and bicarbonate (HCO) levels. Acidosis affects millions annually, resulting in decreased bone mineral density and bone volume and an increased rate of fracture.

Proteasome subunit α1 overexpression preferentially drives canonical proteasome biogenesis and enhances stress tolerance in yeast.

The 26S proteasome conducts the majority of regulated protein catabolism in eukaryotes. At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two β-rings sandwiched between two α-rings. Whereas canonical CPs contain α-rings with seven subunits arranged α1-α7, a non-canonical CP in which a second copy of the α4 subunit replaces the α3 subunit occurs in both yeast and humans.

An Allosteric Interaction Network Promotes Conformation State-Dependent Eviction of the Nas6 Assembly Chaperone from Nascent 26S Proteasomes.

The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes.

Autophagic clearance of proteasomes in yeast requires the conserved sorting nexin Snx4.

Turnover of the 26S proteasome by autophagy is an evolutionarily conserved process that governs cellular proteolytic capacity and eliminates inactive particles. In most organisms, proteasomes are located in both the nucleus and cytoplasm. However, the specific autophagy routes for nuclear and cytoplasmic proteasomes are unclear.