From Powerhouse to Perpetrator—Mitochondria in Health and Disease

Fakouri, Nima Borhan; Hansen, Thomas Lau; Desler, Claus; Anugula, Sharath; Rasmussen, Lene Juel

doi:10.3390/biology8020035

Cited by 12 publications

(11 citation statements)

References 135 publications

(170 reference statements)

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“…However, a deeper understanding of the role of natural metabolites as signaling molecules—metabokines [11]—and molecules regulated by exercise—exerkines and exosomes [113,114,115]—that regulate the completion of the healing cycle holds promise for preventing, slowing, and perhaps reversing [47] some of the effects of aging. Interventions that exploit purinergic [20] and sphingolipid [116] signaling pathways may be particularly powerful since over half of all mitochondrial proteins are regulated by ATP, NAD+, and related nucleotides (Table S1), and many of the molecular hallmarks of aging trace to or regulate the interplay between purines, mitochondria, sphingolipids [117,118], and the nucleus [119].…”

Section: Discussionmentioning

confidence: 99%

Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response

Naviaux

2019

Biology

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The rate of biological aging varies cyclically and episodically in response to changing environmental conditions and the developmentally-controlled biological systems that sense and respond to those changes. Mitochondria and metabolism are fundamental regulators, and the cell is the fundamental unit of aging. However, aging occurs at all anatomical levels. At levels above the cell, aging in different tissues is qualitatively, quantitatively, and chronologically distinct. For example, the heart can age faster and differently than the kidney and vice versa. Two multicellular features of aging that are universal are: (1) a decrease in physiologic reserve capacity, and (2) a decline in the functional communication between cells and organ systems, leading to death. Decreases in reserve capacity and communication impose kinetic limits on the rate of healing after new injuries, resulting in dyssynchronous and incomplete healing. Exercise mitigates against these losses, but recovery times continue to increase with age. Reinjury before complete healing results in the stacking of incomplete cycles of healing. Developmentally delayed and arrested cells accumulate in the three stages of the cell danger response (CDR1, 2, and 3) that make up the healing cycle. Cells stuck in the CDR create physical and metabolic separation—buffer zones of reduced communication—between previously adjoining, synergistic, and metabolically interdependent cells. Mis-repairs and senescent cells accumulate, and repeated iterations of incomplete cycles of healing lead to progressively dysfunctional cellular mosaics in aging tissues. Metabolic cross-talk between mitochondria and the nucleus, and between neighboring and distant cells via signaling molecules called metabokines regulates the completeness of healing. Purinergic signaling and sphingolipids play key roles in this process. When viewed against the backdrop of the molecular features of the healing cycle, the incomplete healing model provides a new framework for understanding the hallmarks of aging and generates a number of testable hypotheses for new treatments.

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Section: Discussionmentioning

confidence: 99%

Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response

Naviaux

2019

Biology

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“…Moreover, mitochondrial-generated ROS and metabolites act as signaling molecules and cofactors that regulate fundamental nuclear processes. Excessive ROS production can induce cellular oxidative stress and damage cellular components and macromolecules, including DNA [39].…”

Section: Mitochondria and Oxidative Stress Generation In Biologicamentioning

confidence: 99%

Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis

Migliaccio

Gregorio

Putti

et al. 2019

Cells

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In our modern society, exposure to stressful environmental stimuli, such as pollutants and/or chronic high-fat feeding, continuously induce tissular/organ metabolic adaptation to promote cellular survival. In extreme conditions, cellular death and tissular/organ damage occur. Mitochondria, as a cellular energy source, seem to play an important role in facing cellular stress induced by these environmental stimuli. On the other hand, mitochondrial dysfunction and oxidative stress play a key role in environmental stress-induced metabolic diseases. However, little is known about the combined effect of simultaneous exposure to chronic high-fat feeding and environmental pollutants on metabolic alterations at a tissular and cellular level, including mitochondrial dysfunction and oxidative stress induction. Our research group recently addressed this topic by analysing the effect of chronic exposure to a non-toxic dose of the environmental pollutant dichlorodiphenyldichloroethylene (DDE) associated with high-fat feeding in male Wistar rats. In this review, we mainly summarize our recent findings on mitochondrial adaptive response and oxidative stress induction in the liver, the main tissue involved in fat metabolism and pollutant detoxification, and in male gonads, the main targets of endocrine disruption induced by both high-fat feeding and environmental pollutants.

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“…The next article by Nima B. Fakouri, Thomas Lau Hansen, Claus Desler, Sharath Anugula and Lene Juel Rasmussen [10] addresses the interactions between mitochondria and cancer. The authors focus their review on genomic instability, dysregulation of cellular energetics, and mitochondrial function.…”

mentioning

confidence: 99%