Role of Signaling Molecules in Mitochondrial Stress Response

Hill, Shauna; Sataranatarajan, Kavithalakshmi; Remmen, Holly Van

doi:10.3389/fgene.2018.00225

Cited by 22 publications

(12 citation statements)

References 108 publications

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“…Additionally, by activating metabolic genes, the mtUPR alters mitochondrial metabolism [115,119]. Furthermore, it has been shown that mitochondria can regulate cell function and cellular metabolism by releasing peptides that are encoded by the short open frames (sORFs) in the mitochondria genome [120].…”

Section: Pathways Dependent On Rosmentioning

confidence: 99%

The secret messages between mitochondria and nucleus in muscle cell biology

Soledad¹,

Charles²,

Das³

2019

Archives of Biochemistry and Biophysics

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Over two thousand proteins are found in the mitochondrial compartment but the mitochondrial genome codes for only 13 proteins. The majority of mitochondrial proteins are products of nuclear genes and are synthesized in the cytosol, then translocated into the mitochondria. Most of the subunits of the five respiratory chain complexes in the inner mitochondrial membrane, which generate a proton gradient across the membrane and produce ATP, are encoded by nuclear genes. Therefore, it is quite clear that import of nuclear-encoded proteins into the mitochondria is essential for mitochondrial function. Nuclear to mitochondrial communication is well studied. However, there is another arm to this communication, mitochondria to nucleus retrograde signaling. This plays an important role in the maintenance of cellular homeostasis, and is less well studied. Several transcription factors, including Sp1, SIRT3 and GSP2, are activated by altered mitochondrial function. These activated transcription factors then translocate to the nucleus. Based on the mitochondrially generated molecular signal, nuclear genes are targeted, which alters transcription of nuclear genes that code for mitochondrial proteins. This review article will mainly focus on this interactive and bi-directional communication between mitochondria and nucleus, and how this communication plays a significant role in muscle cell biology.

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Section: Pathways Dependent On Rosmentioning

confidence: 99%

The secret messages between mitochondria and nucleus in muscle cell biology

Soledad¹,

Charles²,

Das³

2019

Archives of Biochemistry and Biophysics

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“…TFAM is an important mediator of mitochondrial damage-associated molecular patterns and can further regulate inflammation and immunity. 105 TFAM is an important regulator of mtDNA replication. Recently, it was found that a TFAM-mediated increase in mtDNA copy number is important to promote cancer progression by enhancing OXPHOS in microsatellite-stable colorectal cancer.…”

Section: Mitochondrial Dysfunction Contributes To Cancer Malignant Prmentioning

confidence: 99%

Role of the mitochondrial stress response in human cancer progression

Wang

Chen

Tseng

et al. 2020

Exp Biol Med (Maywood)

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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.

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“…To orchestrate the vastly complex cellular system, communication between organelles is paramount . Mitochondria act as a cellular hub that senses and integrates environmental changes, and as a coordinator of adaptive responses through constant communication with other cellular compartments, including the nucleus, regulate key cellular processes that have a significant impact on health span and life span . Many of the known mitochondrial communication mechanisms include those that respond to cellular stress and help to maintain cellular homeostasis .…”

Section: How Do Mitochondria Communicate?mentioning

confidence: 99%

“…To date, eight different MDPs have been reported, including HN, SHLP1–6 (small HN‐like peptides 1–6), and MOTS‐c . Although the genetics of MDP expression is currently being investigated by several groups, it is clear that each MDP has distinct and redundant functions …”

Section: Regulatory Peptides Encoded In the Mitochondrial Genome: Newmentioning

confidence: 99%

MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

Benayoun

Lee

2019

BioEssays

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Mitochondria are increasingly being recognized as information hubs that sense cellular changes and transmit messages to other cellular components, such as the nucleus, the endoplasmic reticulum (ER), the Golgi apparatus, and lysosomes. Nonetheless, the interaction between mitochondria and the nucleus is of special interest because they both host part of the cellular genome. Thus, the communication between genome‐bearing organelles would likely include gene expression regulation. Multiple nuclear‐encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, no mitochondrial‐encoded factors are known to actively regulate nuclear gene expression. MOTS‐c (mitochondrial open reading frame of the 12S ribosomal RNA type‐c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS‐c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis. It is hypothesized that cellular fitness requires the coevolved mitonuclear genomes to coordinate adaptive responses using gene‐encoded factors that cross‐regulate the opposite genome. This suggests that cellular gene expression requires the bipartite split genomes to operate as a unified system, rather than the nucleus being the sole master regulator.

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Role of Signaling Molecules in Mitochondrial Stress Response

Cited by 22 publications

References 108 publications

The secret messages between mitochondria and nucleus in muscle cell biology

The secret messages between mitochondria and nucleus in muscle cell biology

Role of the mitochondrial stress response in human cancer progression

MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

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