Giant Mitochondria in the Myocardium of Aging and Endurance-Trained Mice

Coleman, Raymond; Silbermann, Michael; Gershon, David; Reznick, Abraham Z.

doi:10.1159/000212851

Cited by 76 publications

(51 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In mammals, the proteins regulating giant mitochondria formation are still not identified, although giant mitochondria were reported to be normally observed in the aged or some diseased mammalian cells. [29][30][31][32][33] Our data suggest that Mic60/Mitofilin is a key factor in regulating the formation of giant mitochondria in mammals. In addition, it will be interesting in the future studies to demonstrate how downregulation of Mic60/Mitofilin destabilizes some mitochondrial fusion or fission factors.…”

Section: Discussionmentioning

confidence: 67%

“…27,28 The giant mitochondria, which are enlarged spherical mitochondria, were rare in normal cells, but were observed more frequently in aged or diseased cells. [29][30][31][32][33] Yeast cells lacking Mdm10, Mdm12, Mdm1, Mdm31 or Mdm32 harbor giant mitochondria with abnormal internal structure and mitochondrial DNA (mtDNA) nucleoids; [34][35][36][37] however, no mammalian homologs of Mdm10, Mdm12, Mdm1, Mdm31 or Mdm32 are identified, and the functions and molecular mechanisms for the formation of giant mitochondria in mammals remain poorly understood.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

et al. 2015

View full text Add to dashboard Cite

The MICOS complex (mitochondrial contact site and cristae organizing system) is essential for mitochondrial inner membrane organization and mitochondrial membrane contacts, however, the molecular regulation of MICOS assembly and the physiological functions of MICOS in mammals remain obscure. Here, we report that Mic60/Mitofilin has a critical role in the MICOS assembly, which determines the mitochondrial morphology and mitochondrial DNA (mtDNA) organization. The downregulation of Mic60/Mitofilin or Mic19/CHCHD3 results in instability of other MICOS components, disassembly of MICOS complex and disorganized mitochondrial cristae. We show that there exists direct interaction between Mic60/Mitofilin and Mic19/CHCHD3, which is crucial for their stabilization in mammals. Importantly, we identified that the mitochondrial i-AAA protease Yme1L regulates Mic60/Mitofilin homeostasis. Impaired MICOS assembly causes the formation of 'giant mitochondria' because of dysregulated mitochondrial fusion and fission. Also, mtDNA nucleoids are disorganized and clustered in these giant mitochondria in which mtDNA transcription is attenuated because of remarkable downregulation of some key mtDNA nucleoid-associated proteins.Together, these findings demonstrate that Mic60/Mitofilin homeostasis regulated by Yme1L is central to the MICOS assembly, which is required for maintenance of mitochondrial morphology and organization of mtDNA nucleoids. Mitochondria have a key role in oxidative phosphorylation and related cellular metabolism, in energy conversion, in programmed cell death, in cell growth and in diseases. Mitochondrial outer and inner membranes strongly differ in architecture and functions. The mitochondrial outer membrane forms a barrier to cytosol, and contains channels and the translocases of outer membrane, which is the main protein entry gate of mitochondria. 1,2 In contrast, the mitochondrial inner membrane consists of two morphologically distinct regions: the inner boundary membrane is in close proximity to the outer membrane and the cristae membranes that are large tubular invaginations. [3][4][5][6][7][8] The mitochondrial inner boundary and cristae membrane are physically separated by cristae junctions, which are narrow tubular or slot-like structure. 4,9 The mitochondrial cristae are arranged in regular arrays and are the main sites of ATP production in the mitochondria, but the molecules that are associated with the maintenance of cristae architecture still remain elusive. Recently, several groups identified a large protein complex, MICOS complex (mitochondrial contact site and cristae organizing system; previously named MINOS, MitOS, Mitofilin or Fcj1 complex ), that has a crucial role in the formation of cristae junctions, contact sites to the outer membrane, and the organization of inner membrane. [10][11][12][13][14] In yeast, MICOS consists of at least six subunits: Mic60 (Fcj1), Mic10 (Mio10/Mcs10/Mos1), Mic19 (Aim13/Mcs19), Mic26 (Mio27/Mcs29/Mos2), Mic12 (Aim5/ Msc12) and Mic27 (Aim37/Mcs27). In mammals, five s...

show abstract

Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 99%

Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Mitochondria in aged post-mitotic cells are enlarged and structurally deteriorated, showing swelling and loss of cristae, and are deficient in ATP production. 17,18 These senescent-like abnormalities of mitochondria in autophagy-deficient cardiomyocytes might be responsible for cardiac dysfunction at 10 months of age.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of autophagy in the heart induces age-related cardiomyopathy

Taneike¹,

Yamaguchi²,

Nakai³

et al. 2010

Autophagy

410

326

View full text Add to dashboard Cite

“…Many mitochondria in aged post-mitotic cells are enlarged and structurally deteriorated, showing swelling and disintegration of cristae, often resulting in the formation of amorphous material. 90,91 Excessively enlarged mitochondria are usually called 'giant'. 90 Senescent mitochondria are defective in ATP production 92 and are reported to produce increased amounts of reactive oxygen species (ROS), 93 which are harmful for cells and nevertheless cannot be eliminated.…”

Section: General Consequences Of Autophagic Failurementioning

confidence: 99%

“…90,91 Excessively enlarged mitochondria are usually called 'giant'. 90 Senescent mitochondria are defective in ATP production 92 and are reported to produce increased amounts of reactive oxygen species (ROS), 93 which are harmful for cells and nevertheless cannot be eliminated. The mechanisms underlying age-related mitochondrial changes are still debated.…”

Section: General Consequences Of Autophagic Failurementioning

confidence: 99%

Autophagy and Aging: The Importance of Maintaining "Clean" Cells

et al. 2005

View full text Add to dashboard Cite

Previously published online as an Autophagy E-publication: http://www.landesbioscience.com/journals/autophagy/abstract.php?id=2017 KEY WORDS Review Autophagy and AgingThe Importance of Maintaining "Clean" Cells ABSTRACTA decrease in the turnover of cellular components and the intracellular accumulation of altered macromolecules and organelles are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. In this work we review the molecular defects responsible for the malfunctioning of two forms of autophagy, macroautophagy and chaperone-mediated autophagy, in old mammals, and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. These and other possible experimental restorative efforts are discussed.

show abstract

Giant Mitochondria in the Myocardium of Aging and Endurance-Trained Mice

Cited by 76 publications

References 18 publications

Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

Inhibition of autophagy in the heart induces age-related cardiomyopathy

Autophagy and Aging: The Importance of Maintaining "Clean" Cells

Contact Info

Product

Resources

About