Biology subjects

Schuler, M.-H.

Publications and source records attributed to Schuler, M.-H..

2 recordsLinked to original sources

bioRxiv2026

The multistep quality control of mitochondrial β-barrel protein import

Mitochondrial {beta}-barrel proteins fulfill essential functions for cell viability including transport of proteins, ions and metabolites across the outer membrane. The translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex) transport these proteins into the outer membrane. Although {beta}-barrel proteins are essential for cell viability, the quality control mechanisms that monitor their import into the outer membrane remain unknown. We uncovered that Msp1 and Ubx2-recruited Cdc48 cooperate to remove a SAM-arrested Tom40 variant. Prior to degradation, the {beta}-barrel protein is deposited in cytosolic protein storages, termed MitoStores, to minimize accumulation of aberrant proteins in the cell. The cytosolic AAA ATPase Hsp104 disaggregates these proteins to facilitate their proteasomal degradation. Altogether, mitochondrial and cytosolic factors cooperate to degrade translocation-arrested mitochondrial {beta}-barrel proteins.

molecular biology↗

bioRxiv2020

Mitochondrial-Derived Compartments Facilitate Cellular Adaptation to Amino Acid Stress

Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), is a dynamic, lumen-containing organelle that functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and remove Tom70, a surface receptor required for import of nutrient carriers of the SLC25 family. MDC formation is regulated by levels of mitochondrial carriers, and its activation by amino acids occurs simultaneously with removal of plasma membrane-localized transporters via the multi-vesicular body (MVB) pathway. Combined loss of MDC and MVB formation renders cells sensitive to elevated amino acids, suggesting these pathways operate as a coordinated network to protect cells from amino acid toxicity.

cell biology↗