Biology subjects

Baile, M. G.

Publications and source records attributed to Baile, M. G..

3 recordsLinked to original sources

bioRxiv2023

Conserved cardiolipin-mitochondrial ADP/ATP carrier interactions assume distinct structural and functional roles that are clinically relevant

The mitochondrial phospholipid cardiolipin (CL) promotes bioenergetics via oxidative phosphorylation (OXPHOS). Three tightly bound CLs are evolutionarily conserved in the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) which resides in the inner mitochondrial membrane and exchanges ADP and ATP to enable OXPHOS. Here, we investigated the role of these buried CLs in the carrier using yeast Aac2 as a model. We introduced negatively charged mutations into each CL-binding site of Aac2 to disrupt the CL interactions via electrostatic repulsion. While all mutations disturbing the CL-protein interaction destabilized Aac2 monomeric structure, transport activity was impaired in a pocket-specific manner. Finally, we determined that a disease-associated missense mutation in one CL-binding site in ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

biochemistry↗

bioRxiv2021

A PX-BAR protein Mvp1/SNX8 and a dynamin-like GTPase Vps1 drive endosomal recycling

Membrane protein recycling systems are essential for maintenance of the endosome-lysosome system. In yeast, retromer and Snx4 coat complexes are recruited to the endosomal surface where they recognize cargos. They sort cargo and deform the membrane into recycling tubules that bud from the endosome and target to the Golgi. Here, we reveal that the SNX-BAR protein, Mvp1, mediates an endosomal recycling pathway which is mechanistically distinct from the retromer and Snx4 pathways. Mvp1 deforms the endosomal membrane and sorts cargos containing a specific sorting motif into a membrane tubule. Subsequently, Mvp1 recruits the dynamin-like GTPase Vps1 to catalyze membrane scission and release of the recycling tubule. Similarly, SNX8, the human homolog of Mvp1, which has been also implicated in Alzheimers disease, mediates formation of an endosomal recycling tubule. Thus, we present evidence for a novel endosomal retrieval pathway that is conserved from yeast to humans. In BriefPX-BAR Mvp1 and dynamin-like GTPase Vps1 drive retromer independent endosomal recycling. HighlightsO_LIRetromer- and Snx4-independent endosomal recycling pathway discovered C_LIO_LISNX-BAR Mvp1 and dynamin-like GTPase Vps1 mediate cargo sorting into recycling tubules/vesicles in the absence of retromer function C_LIO_LIMvp1 together with retromer and Snx4 complexes contribute to proper endosome function C_LIO_LIMvp1 mediated recycling is evolutionary conserved from yeast to humans C_LIO_LICharacters: 43,934/45,000 (including spaces and main figure legends but excluding STAR Methods text, supplemental item legends, and References section) C_LI

cell biology↗

bioRxiv2019

The yeast Art1 arrestin domain contains disordered insertions that regulate its localization and activity

The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins which, in the yeast Saccharomyces cerevisiae, is mediated by the HECT E3 ubiquitin ligase Rsp5 and arrestin-related trafficking (ART) adaptors. Here, we provide evidence that an ART family member, Art1, consists of an arrestin fold with extended N- and C-terminal tails, and interspersed with loop insertions. These loop and tail regions, while not strictly required for Art1 function, regulate its activity through two separate mechanisms. One loop mediates Art1 cargo specificity. Other loops are subjected to phosphorylation in a manner dependent on the Pho85 cyclins Clg1 and Pho80. Phosphorylation of the loops controls Art1s localization to the plasma membrane, which promotes cargo ubiquitylation and endocytosis, demonstrating a mechanism through which Art1 activity is regulated.

cell biology↗