Article
Biochemistry & Molecular Biology
Victor V. Lemeshko
Summary: Recently reported kinase-linked mild depolarization of mitochondria may be a crucial component of the mitochondrial anti-aging program. However, the current measurement methods for mitochondrial inner membrane potential ignore the possibility of outer membrane potential generation. The experimental data reported in this study may reflect changes in the positive outer membrane potential generated by VDAC-kinase complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Biology
Hong Qi, Yu-Song Yin, Zhi-Yong Yin, Xiang Li, Jian-Wei Shuai
Summary: Recent studies have found a close relationship between apoptosis and inflammation, but the mechanism linking them through mitochondrial membrane permeabilization is still unclear. In this study, a mathematical model consisting of four functional modules was constructed. Bifurcation analysis revealed bistability caused by Bcl-2 family member interaction, and time series showed a 30-minute time difference between Cyt c and mtDNA release, consistent with previous research. The model predicted that Bax aggregation kinetics determines whether cells undergo apoptosis or inflammation, and altering the inhibitory effect of caspase 3 on IFN-β production allows both apoptosis and inflammation to occur concurrently. This work provides a theoretical framework for exploring the mechanism of mitochondrial membrane permeabilization in controlling cell fate.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yang Xu, Hediye Erdjument-Bromage, Colin K. L. Phoon, Thomas A. Neubert, Mindong Ren, Michael Schlame
Summary: Mitochondrial cristae are crowded with proteins, leading to remodeling of cardiolipin which supports high protein concentration in the inner mitochondrial membrane. Lack of cardiolipin remodeling or biosynthesis results in decreased density of OXPHOS proteins in the membrane.
Article
Biology
Layla Drwesh, Benjamin Heim, Max Graf, Linda Kehr, Lea Hansen-Palmus, Mirita Franz-Wachtel, Boris Macek, Hubert Kalbacher, Johannes Buchner, Doron Rapaport
Summary: This study reconstituted the early cytosolic steps of signal-anchored (SA) protein biogenesis and identified molecular (co)chaperones, including Hsp70, Hsp90, and Hsp40 family co-chaperones, that interact with newly synthesized SA proteins. These interactions are mediated by the hydrophobic transmembrane segments of the SA proteins. The study also demonstrated the inhibitory effect of interfering with these interactions on SA protein biogenesis and successfully reconstituted the transfer of peptides from Hsp70 chaperone to the mitochondrial Tom70 receptor in vitro.
Article
Biochemistry & Molecular Biology
Michael Schlame
Summary: The low lipid-to-protein ratio in the inner mitochondrial membrane leads to an increased hydrophobic coupling between proteins and lipids, necessitating stabilizing mechanisms. Protein supercomplexes and cardiolipin are crucial for maintaining the integrity of the inner mitochondrial membrane by reducing the energy penalty of crowding.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Cell Biology
Chibuike David Obi, Tawhid Bhuiyan, Harry A. Dailey, Amy E. Medlock
Summary: This article discusses the structure, function, and metabolic regulation of ferrochelatase, a key enzyme in heme biosynthesis and mitochondrial heme homeostasis. The review provides insight into the physiological dynamics of ferrochelatase and its role in the transport and synthesis of heme in eukaryotic cells. It also explores the regulatory mechanisms and inhibition of ferrochelatase, as well as its significance in protozoal parasites.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Microbiology
Jessica L. Keffer, Sean M. McAllister, Arkadiy I. Garber, Beverly J. Hallahan, Molly C. Sutherland, Sharon Rozovsky, Clara S. Chan
Summary: Iron (Fe) oxidation is a crucial biogeochemical process on Earth, with microbial iron oxidizers playing a significant role. Studies on Cyc2 in neutrophilic iron oxidizers suggest that it functions as an iron oxidase, providing new insights into the metabolism of these organisms. The presence of Cyc2 in a wide variety of iron oxidizers indicates its importance in iron oxidation processes.
Article
Multidisciplinary Sciences
Kazuya Nishio, Tomoyuki Kawarasaki, Yuki Sugiura, Shunsuke Matsumoto, Ayano Konoshima, Yuki Takano, Mayuko Hayashi, Fumihiko Okumura, Takumi Kamura, Tsunehiro Mizushima, Kunio Nakatsukasa
Summary: Deficiencies in mitochondrial protein import are associated with diseases, but it is unclear how accumulation of non-imported mitochondrial proteins causes cell dysfunction. This study showed that non-imported citrate synthase is targeted for proteasomal degradation. Accumulation of non-imported citrate synthase caused ectopic citrate synthesis, leading to metabolic imbalance and growth defect. This study highlights the importance of mitochondrial import and its failure in cellular metabolism.
Article
Microbiology
Jinna Bai, Nicole Raustad, Jason Denoncourt, Tim van Opijnen, Edward Geisinger
Summary: This study analyzed the defense mechanism of A. baumannii against phage using high-throughput genetics and found that inducing overproduction of capsule makes bacteria highly susceptible to phage, while turning off the stress response or mutating the capsule structure causes complete resistance. Modulating other surface structures and intracellular protease also increases phage attack. This study reveals the connection between phage pressure and the evolution of virulence in A. baumannii, and provides insights for improving phage-based antimicrobial therapies.
Article
Biochemistry & Molecular Biology
Jonathan V. Dietz, Mathilda M. Willoughby, Robert B. Piel III, Teresa A. Ross, Iryna Bohovych, Hannah G. Addis, Jennifer L. Fox, William N. Lanzilotta, Harry A. Dailey, James A. Wohlschlegel, Amit R. Reddi, Amy E. Medlock, Oleh Khalimonchuk
Summary: Heme is an essential cofactor for cellular processes in eukaryotes. The biosynthesis of heme in yeast is regulated by the mitochondrial component Mic60, with loss of this component impacting enzyme activity and leading to accumulation of potentially toxic precursors.
Article
Biochemistry & Molecular Biology
Victor V. Lemeshko
Summary: Mitochondria, composed of two membranes, play a key role in energy production in eukaryotic cells. The outer membrane controls the energy flux and exchange of metabolites, while the inner membrane is responsible for oxidative phosphorylation. Voltage-dependent anion channels (VDACs) facilitate the transport of metabolites across the outer membrane. This study analyzes experimental data related to targeting VDACs and VDAC-kinase complexes, expanding on the hypothesis of outer membrane potential (OMP) generation and its effect on cell energy metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Review
Biochemistry & Molecular Biology
Jean-Francois Trempe, Kalle Gehring
Summary: Parkinson's disease (PD) is becoming a looming public health crisis as the global population ages. Breakthroughs in understanding the genetic forms related to dysfunctional mitochondria have opened new avenues for therapeutic interventions in PD, by studying the proteins PINK1 and parkin and their molecular mechanisms for recognizing and controlling these damaged mitochondria.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Jialin Zhou, Martin Jung, Kai S. Dimmer, Doron Rapaport
Summary: In this study, we investigated the biogenesis of multi-span proteins in the mitochondrial outer membrane. Our findings suggest that the targeting specificity and efficiency of these proteins are influenced by their length, as well as the behavior of the membrane. Additionally, cytosolic proteins do not significantly contribute to the biogenesis process.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Varnesh Tiku, Eric M. Kofoed, Donghong Yan, Jing Kang, Min Xu, Mike Reichelt, Ivan Dikic, Man-Wah Tan
Summary: Acinetobacter baumannii utilizes the release of outer membrane vesicles containing OmpA(Ab) to promote pathogenesis, activating DRP1 in mammalian cells and leading to mitochondrial fragmentation, ROS production, and cell death. OmpA(Ab) is also essential for systemic dissemination in a mouse lung infection model, highlighting its role as a virulence factor.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Siqi Liu, Shanshan Liu, Baiyu He, Lanlan Li, Lin Li, Jiawen Wang, Tao Cai, She Chen, Hui Jiang
Summary: The research reveals that yeast mutants deficient in certain oxidative phosphorylation complexes and mtDNA exhibit progressive reduction of mitochondrial membrane potential. These mutants activate adaptive responses, including remodeling of mitochondrial proteome and reshaping of cellular metabolism.