scholarly journals Multifaceted Roles of Mitochondrial Stress Responses under ETC Dysfunction – Repair, Destruction and Pathogenesis

FEBS Journal ◽  
2021 ◽  
Author(s):  
Shanshan Liu ◽  
Siqi Liu ◽  
Hui Jiang
Keyword(s):  
Stress Responses ◽  
Mitochondrial Stress

scholarly journals Correction: Drp1 modulates mitochondrial stress responses to mitotic arrest

2021 ◽  
Author(s):  
Aida Peña-Blanco ◽  
Manuel D. Haschka ◽  
Andreas Jenner ◽  
Theresia Zuleger ◽  
Tassula Proikas-Cezanne ◽  
...  
Keyword(s):  
Stress Responses ◽  
Mitotic Arrest ◽  
Mitochondrial Stress

scholarly journals Complex IV-deficient Surf1−/− mice initiate mitochondrial stress responses

2014 ◽  
Vol 462 (2) ◽  
pp. 359-371 ◽  
Author(s):  
Daniel A. Pulliam ◽  
Sathyaseelan S. Deepa ◽  
Yuhong Liu ◽  
Shauna Hill ◽  
Ai-Ling Lin ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Complex Iv ◽  
Mitochondrial Stress ◽  
Nrf2 Pathway ◽  
Compensatory Responses ◽  
Unfolded Protein ◽  
Assembly Factor ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

Loss of complex IV assembly factor SURF1 in mice results in compensatory responses including mitochondrial biogenesis, the Nrf2 pathway and the mitochondrial unfolded protein response. These compensatory responses may contribute to the lack of deleterious phenotypes under basal conditions.

scholarly journals A conserved role of CBP/p300 in mitochondrial stress response and longevity

2020 ◽  
Author(s):  
Terytty Yang Li ◽  
Maroun Bou Sleiman ◽  
Hao Li ◽  
Arwen W. Gao ◽  
Adrienne Mottis ◽  
...  
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Amyloid Β ◽  
Human Populations ◽  
Histone Demethylases ◽  
Mitochondrial Stress ◽  
Unfolded Protein ◽  
Evolutionarily Conserved ◽  
Protein Response

Abstract Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPRmt). However, how different layers of UPRmt regulators are orchestrated to transcriptionally activate the stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator for UPRmt activation, as well as for mitochondrial stress-induced immune response, reduction of amyloid-β aggregation and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPRmt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPRmt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPRmt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPRmt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.

scholarly journals Primary cilia mediate mitochondrial stress responses to promote dopamine neuron survival in a Parkinson’s disease model

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Ji-Eun Bae ◽  
Gil Myung Kang ◽  
Se Hee Min ◽  
Doo Sin Jo ◽  
Yong-Keun Jung ◽  
...  
Keyword(s):  
Cell Survival ◽  
Stress Responses ◽  
Primary Cilia ◽  
Control Cell ◽  
Disease Model ◽  
Reactive Oxygen Species Generation ◽  
Neuronal Loss ◽  
Dopamine Neurons ◽  
Mitochondrial Stress ◽  
Motor Disability

AbstractA primary cilium is an antenna-like structure on the cell surface that plays a crucial role in sensory perception and signal transduction. Mitochondria, the ‘powerhouse’ of the cell, control cell survival, and death. The cellular ability to remove dysfunctional mitochondria through mitophagy is important for cell survival. We show here that mitochondrial stress, caused by respiratory complex inhibitors and excessive fission, robustly stimulates ciliogenesis in different types of cells including neuronal cells. Mitochondrial stress-induced ciliogenesis is mediated by mitochondrial reactive oxygen species generation, subsequent activation of AMP-activated protein kinase and autophagy. Conversely, abrogation of ciliogenesis compromises mitochondrial stress-induced autophagy, leading to enhanced cell death. In mice, treatment with mitochondrial toxin, MPTP elicits ciliary elongation and autophagy in the substantia nigra dopamine neurons. Blockade of cilia formation in these neurons attenuates MPTP-induced autophagy but facilitates dopamine neuronal loss and motor disability. Our findings demonstrate the important role of primary cilia in cellular pro-survival responses during mitochondrial stress.

scholarly journals Role of the mitochondrial stress response in human cancer progression

2020 ◽  
Vol 245 (10) ◽  
pp. 861-878 ◽  
Author(s):  
Sheng-Fan Wang ◽  
Shiuan Chen ◽  
Ling-Ming Tseng ◽  
Hsin-Chen Lee
Keyword(s):  
Stress Response ◽  
Mitochondrial Dysfunction ◽  
Cancer Progression ◽  
Stress Responses ◽  
Retrograde Signaling ◽  
Cancer Targeting ◽  
Mitochondrial Stress ◽  
Unfolded Protein ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

Mitochondria are important organelles that are responsible for cellular energy metabolism, cellular redox/calcium homeostasis, and cell death regulation in mammalian cells. Mitochondrial dysfunction is involved in various diseases, such as neurodegenerative diseases, cardiovascular diseases, immune disorders, and cancer. Defective mitochondria and metabolism remodeling are common characteristics in cancer cells. Several factors, such as mitochondrial DNA copy number changes, mitochondrial DNA mutations, mitochondrial enzyme defects, and mitochondrial dynamic changes, may contribute to mitochondrial dysfunction in cancer cells. Some lines of evidence have shown that mitochondrial dysfunction may promote cancer progression. Here, several mitochondrial stress responses, including the mitochondrial unfolded protein response and the integrated stress response, and several mitochondrion-derived molecules (reactive oxygen species, calcium, oncometabolites, and others) are reviewed; these pathways and molecules are considered to act as retrograde signaling regulators in the development and progression of cancer. Targeting these components of the mitochondrial stress response may be an important strategy for cancer treatment. Impact statement Dysregulated mitochondria often occurred in cancers. Mitochondrial dysfunction might contribute to cancer progression. We reviewed several mitochondrial stresses in cancers. Mitochondrial stress responses might contribute to cancer progression. Several mitochondrion-derived molecules (ROS, Ca2+, oncometabolites, exported mtDNA, mitochondrial double-stranded RNA, humanin, and MOTS-c), integrated stress response, and mitochondrial unfolded protein response act as retrograde signaling pathways and might be critical in the development and progression of cancer. Targeting these mitochondrial stress responses may be an important strategy for cancer treatment.

scholarly journals Drp1 modulates mitochondrial stress responses to mitotic arrest

2020 ◽  
Vol 27 (9) ◽  
pp. 2620-2634 ◽  
Author(s):  
Aida Peña-Blanco ◽  
Manuel D. Haschka ◽  
Andreas Jenner ◽  
Theresia Zuleger ◽  
Tassula Proikas-Cezanne ◽  
...  
Keyword(s):  
Stress Responses ◽  
Mitotic Arrest ◽  
Mitochondrial Stress

scholarly journals Mitochondrial Metabolic Signatures in Hepatocellular Carcinoma

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1901
Author(s):  
Ho-Yeop Lee ◽  
Ha Thi Nga ◽  
Jingwen Tian ◽  
Hyon-Seung Yi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mitochondrial Dysfunction ◽  
Stress Responses ◽  
Metabolic Reprogramming ◽  
Ros Production ◽  
Unfolded Proteins ◽  
Mitochondrial Stress ◽  
Unfolded Protein ◽  
Protein Response ◽  
Metabolic Signatures

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. HCC progression and metastasis are closely related to altered mitochondrial metabolism, including mitochondrial stress responses, metabolic reprogramming, and mitoribosomal defects. Mitochondrial oxidative phosphorylation (OXPHOS) defects and reactive oxygen species (ROS) production are attributed to mitochondrial dysfunction. In response to oxidative stress caused by increased ROS production, misfolded or unfolded proteins can accumulate in the mitochondrial matrix, leading to initiation of the mitochondrial unfolded protein response (UPRmt). The mitokines FGF21 and GDF15 are upregulated during UPRmt and their levels are positively correlated with liver cancer development, progression, and metastasis. In addition, mitoribosome biogenesis is important for the regulation of mitochondrial respiration, cell viability, and differentiation. Mitoribosomal defects cause OXPHOS impairment, mitochondrial dysfunction, and increased production of ROS, which are associated with HCC progression in mouse models and human HCC patients. In this paper, we focus on the role of mitochondrial metabolic signatures in the development and progression of HCC. Furthermore, we provide a comprehensive review of cell autonomous and cell non-autonomous mitochondrial stress responses during HCC progression and metastasis.

scholarly journals Visualising formation of the ribosomal active site in mitochondria

2021 ◽  
Author(s):  
Viswanathan Chandrasekaran ◽  
Nirupa Desai ◽  
Nicholas O. Burton ◽  
Hanting Yang ◽  
Jon Price ◽  
...  
Keyword(s):  
Stress Responses ◽  
Large Subunit ◽  
Mitochondrial Protein ◽  
Mitochondrial Stress ◽  
Cryo Electron Microscopy ◽  
Complex Process ◽  
Mitochondrial Ribosome ◽  
Peptidyl Transferase Centre

SummaryRibosome assembly is an essential and complex process that is regulated at each step by specific biogenesis factors. Using cryo-electron microscopy, we identify and order major steps in the formation of the highly conserved peptidyl transferase centre (PTC) and tRNA binding sites in the large subunit of the human mitochondrial ribosome (mitoribosome). The conserved GTPase GTPBP7 regulates the folding and incorporation of core 16S ribosomal RNA (rRNA) helices and the ribosomal protein bL36m, and ensures that the PTC base U3039 has been 2′-O-methylated. Additionally, GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which facilitate earlier steps by sequestering H68-71 of the 16S rRNA and allowing biogenesis factors to access the maturing PTC. Consistent with the central role of NSUN4•MTERF4 and GTPBP7 during mitoribosome biogenesis, in vivo mutagenesis designed to disrupt binding of their Caenorhabditis elegans orthologs to the large subunit potently activates mitochondrial stress responses and results in severely reduced viability, developmental delays and sterility. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4 but not its enzymatic activity, is indispensable for mitochondrial protein synthesis in metazoans.

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