Mitochondrial adventures at the organelle society

Diogo, Cátia V.; Yambire, King Faisal; Mosquera, Lorena Fernández; Branco, F.T.; Raimundo, Nuno

doi:10.1016/j.bbrc.2017.04.124

Cited by 49 publications

(35 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interplay here described between mitochondria and lysosomes brings the issue of organelle cross-talk to center stage. While defects in cellular organelles were studied in an organellespecific manner, it is now clear that to fully understand the impact of one dysfunctional organelle, such as the mitochondria, it is pivotal to understand how the other cellular organelles respond to the mitochondrial defect [13,[65][66][67][68][69]. This is particularly relevant since the existence of contact sites between mitochondria and lysosomes was recently reported in mammalian cells [70].…”

Section: Discussionmentioning

confidence: 99%

“…This question goes beyond fundamental biology, since in many diseases caused by primary malfunction of one organelle (e.g., mitochondrial diseases, lysosomal storage diseases, etc. ), defects in other organelles have been extensively reported [65]. However, it is usually assumed that the secondary perturbations in other organelles occur chaotically and progressively, as eventually every component of a diseased cell would cease to function.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis

et al. 2019

Self Cite

View full text Add to dashboard Cite

Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPKinhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity of the lysosomal Ca 2+ channel MCOLN1 (mucolipin 1). MCOLN1 is regulated by phosphoinositide kinase PIKFYVE and its product PtdIns(3,5)P 2 , which is also decreased in RC-deficiency. Notably, reactivation of AMPK, in a PIKFYVEdependent manner, or of MCOLN1 in RC-deficient cells, restores lysosomal hydrolytic capacity. Building on these data and the literature, we propose that downregulation of the AMPK-PIKFYVE-PtdIns(3,5)P 2-MCOLN1 pathway causes lysosomal Ca 2+ accumulation and impaired lysosomal catabolism. Besides unveiling a novel role of AMPK in lysosomal function, this study points to the mechanism that links mitochondrial malfunction to impaired lysosomal catabolism, underscoring the importance of AMPK and the complexity of organelle cross-talk in the regulation of cellular homeostasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In [3,4]. Interestingly, PHB subunits have been found as transient interactors of the peroxisomal importomer [106], as well as in lipid droplets and lipid rafts preparations [107,108].…”

Section: The Phb Complex In Mitochondrial Turnovermentioning

confidence: 99%

“…However, nowadays we know that mitochondria are acting within an integrated network, communicating with the rest of cellular organelles [1]. Mitochondria are tightly connected with the endoplasmic reticulum (ER) [2] but also with lysosomes, lipid droplets and peroxisomes [3][4][5]. In particular, mitochondria are essential for Ca 2+ homeostasis and Fe-S cluster biogenesis, two processes involved in health [6,7].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex

Hernando‐Rodríguez¹,

Artal‐Sanz²

2018

Preprint

View full text Add to dashboard Cite

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the OXPHOS system for ATP production. It requires, in addition, the import of thousands of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPRmt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial PHB (prohibitin) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

show abstract

“…While these findings suggest that LE/Lys can regulate mitochondrial function, there is also evidence that mitochondrial respiration regulates the biogenesis and function of the LE/Lys compartment (Baixauli et al, 2015 ; Daniele and Schiaffino, 2016 ; Raimundo et al, 2016 ; Diogo et al, 2017 ; Elbaz-Alon, 2017 ). Ablation of mitochondrial oxidative phosphorylation by genetic deletion of mitochondrial transcription factor A in T cells has been shown to regulate lysosomal homeostasis and function.…”

Section: Mitochondria-lysosomal Liaisons In Np Diseasementioning

confidence: 99%

Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease

et al. 2017

View full text Add to dashboard Cite

Lysosomal storage disorders (LSD) are characterized by the accumulation of diverse lipid species in lysosomes. Niemann-Pick type A/B (NPA/B) and type C diseases Niemann-Pick type C (NPC) are progressive LSD caused by loss of function of distinct lysosomal-residing proteins, acid sphingomyelinase and NPC1, respectively. While the primary cause of these diseases differs, both share common biochemical features, including the accumulation of sphingolipids and cholesterol, predominantly in endolysosomes. Besides these alterations in lysosomal homeostasis and function due to accumulation of specific lipid species, the lysosomal functional defects can have far-reaching consequences, disrupting intracellular trafficking of sterols, lipids and calcium through membrane contact sites (MCS) of apposed compartments. Although MCS between endoplasmic reticulum and mitochondria have been well studied and characterized in different contexts, emerging evidence indicates that lysosomes also exhibit close proximity with mitochondria, which translates in their mutual functional regulation. Indeed, as best illustrated in NPC disease, alterations in the lysosomal-mitochondrial liaisons underlie the secondary accumulation of specific lipids, such as cholesterol in mitochondria, resulting in mitochondrial dysfunction and defective antioxidant defense, which contribute to disease progression. Thus, a better understanding of the lysosomal and mitochondrial interactions and trafficking may identify novel targets for the treatment of Niemann-Pick disease.

show abstract

Mitochondrial adventures at the organelle society

Cited by 49 publications

References 84 publications

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis

Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex

Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease

Contact Info

Product

Resources

About