A5085662247- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- Heat shock proteins research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Enzyme Structure and Function
- Endoplasmic Reticulum Stress and Disease
- Animal Virus Infections Studies
- Mechanisms of cancer metastasis
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
University of Freiburg
2021-2025
Universitätsmedizin Göttingen
2015-2021
University of Göttingen
2014-2021
Columbia College
2015
German Primate Center
2014
Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control have been linked to various diseases. Different views exist on the composition of human mitochondrial proteome. We classified >8,000 proteins in preparations cells defined a high-confidence proteome >1,100 (MitoCoP). identified interactors translocases, respiratory chain, ATP synthase assembly factors. The abundance MitoCoP covers six orders magnitude amounts 7% with chaperones HSP60-HSP10...
Highlights•Mitochondrial ribosomes display translational plasticity•COX1 translation in mitochondria is stalled the absence of nuclear-encoded COX4•A ribosome nascent chain complex COX1 a primed state for IV assembly•MITRAC regulates via complexes interactionSummaryMitochondrial translate membrane integral core subunits oxidative phosphorylation system encoded by mtDNA. These products associate with nuclear-encoded, imported proteins to form enzyme that produce ATP. Here, we show human...
Cellular proteostasis requires transport of polypeptides across membranes. Although defective processes trigger cytosolic rescue and quality control mechanisms that clear translocases membranes from unproductive cargo, proteins are synthesized within mitochondria not accessible to these mechanisms. Mitochondrial-encoded inserted cotranslationally into the inner membrane by conserved insertase OXA1L. Here, we identify TMEM126A as a OXA1L-interacting protein. associates with mitochondrial...
Nuclear-encoded mitochondrial proteins destined for the matrix have to be transported across two membranes. The TOM and TIM23 complexes facilitate transport of precursor with N-terminal targeting signals into matrix. During transport, precursors are recognized by complex in inner membrane handover from complex. However, we little knowledge on organization TOM-TIM23 transition zone how transfer between translocases occurs. Here, designed a protein that is stalled during TOM-TIM23-spanning...
Two driving forces energize precursor translocation across the inner mitochondrial membrane. Although membrane potential (Δψ) is considered to drive of positively charged presequences through TIM23 complex (presequence translocase), activity Hsp70-powered import motor crucial for mature protein portion into matrix. In this study, we show that matrix proteins display surprisingly different dependencies on Δψ. However, a precursor's hypersensitivity reduction Δψ not linked respective...
The mitochondrial proteome arises from dual genetic origin. Nuclear-encoded proteins need to be transported across or inserted into two distinguished membranes, and the TOM complex represents main translocase in outer membrane. Its composition regulations have been extensively investigated within yeast cells. However, we little knowledge of human Here, defined interactome a comprehensive manner using biochemical approaches isolate combination with quantitative mass spectrometry analyses....
Virtually all mitochondrial matrix proteins and a considerable number of inner membrane carry positively charged, N-terminal presequence are imported by the TIM23 complex (presequence translocase) located in membrane. The voltage-regulated Tim23 channel constitutes actual protein-import pore wide enough to allow passage polypeptides with secondary structure. In this study, we identify amino acids important for cation selectivity Tim23. Structure based mutants show that is provided highly...
Abstract Reversible acetylation of mitochondrial proteins is a regulatory mechanism central to adaptive metabolic responses. Yet, how such functionally relevant protein achieved remains unexplored. Here we reveal an unprecedented role the MYST family lysine acetyltransferase MOF in energy metabolism via acetylation. Loss MOF–KANSL complex members leads defects including fragmentation, reduced cristae density and impaired electron transport chain IV integrity primary mouse embryonic...
Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of virus public health concern. The spike protein MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation MERS-S by cellular proteases. Proteolytic during uptake target cells has been demonstrated. However, it unclear whether also cleaved S synthesis in infected cleavage required for infectivity. Here, we show that...
The presequence translocase of the mitochondrial inner membrane (TIM23 complex) facilitates anterograde precursor transport into matrix and lateral release precursors with stop-transfer signal (sorting). Sorting requires exit from translocation channel lipid phase through gate TIM23 complex. How two modes are regulated balanced against each other is unknown. Here we show that import motor J-protein Pam18, which essential for import, controls protein bilayer. Constitutively...