Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission

Osellame, Laura D.; Singh, Abeer Prakash; Stroud, David A.; Palmer, Catherine S; Stojanovski, Diana; Ramachandran, Rajesh; Ryan, Michael

doi:10.1242/jcs.185165

Cited by 278 publications

(301 citation statements)

References 63 publications

Supporting

Mentioning

272

Contrasting

Order By: Relevance

“…1B) (Otera et al, 2010;Osellame et al, 2016). Overexpression of Mff induces the recruitment of Drp1 to mitochondria and subsequent mitochondrial fragmentation, whereas its deficiency leads to mitochondrial elongation (Otera et al, 2010).…”

Section: (2) Mitochondrial Fissionmentioning

confidence: 99%

Structure, function, and regulation of mitofusin‐2 in health and disease

2017

View full text Add to dashboard Cite

Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in these molecules are associated with severe neurodegenerative and non-neurological diseases pointing to the importance of functional mitochondrial dynamics in normal cell physiology. In recent years, significant progress has been made in our understanding of mitochondrial dynamics, which has raised interest in defining the physiological roles of key regulators of fusion and fission and led to the identification of additional functions of Mfn2 in mitochondrial metabolism, cell signalling, and apoptosis. In this review, we summarize the current knowledge of the structural and functional properties of Mfn2 as well as its regulation in different tissues, and also discuss the consequences of aberrant Mfn2 expression.

show abstract

Section: (2) Mitochondrial Fissionmentioning

confidence: 99%

Structure, function, and regulation of mitofusin‐2 in health and disease

2017

View full text Add to dashboard Cite

show abstract

“…Mff recruits fission-active Ser616 pDrp1 to mitochondria; dephosphorylation of Drp1 at Ser637 residue is necessary for interaction of Drp1 with Mff (Cereghetti et al, 2008;Chang & Blackstone, 2007;Cribbs & Strack, 2007;Kashatus et al, 2011;Taguchi et al, 2007;Zhang, Liu, Wu, & Xing, 2016). Fis1, though identified first as the mitochondrial adaptor for Drp1, has later been found to be redundant for homeostatic mitochondrial fission and is only associated with stress or chemical-induced mitochondrial division or mitophagy (Lee, Jeong, Karbowski, Smith, & Youle, 2004;Osellame et al, 2016;Otera et al, 2010;Shen et al, 2014;Yamano, Fogel, Wang, van der Bliek, & Youle, 2014;Yoon et al, 2003). Fis1, though identified first as the mitochondrial adaptor for Drp1, has later been found to be redundant for homeostatic mitochondrial fission and is only associated with stress or chemical-induced mitochondrial division or mitophagy (Lee, Jeong, Karbowski, Smith, & Youle, 2004;Osellame et al, 2016;Otera et al, 2010;Shen et al, 2014;Yamano, Fogel, Wang, van der Bliek, & Youle, 2014;Yoon et al, 2003).…”

Section: Drp1-dependent Disruption Of Mitochondrial Network Stimulamentioning

confidence: 99%

Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent mitochondrial fragmentation during infection

Mukherjee

Patra

Bhowmick

et al. 2018

Cellular Microbiology

View full text Add to dashboard Cite

Dynamic equilibrium between mitochondrial fission and mitochondrial fusion serves as an important quality control system within cells ensuring cellular vitality and homeostasis. Viruses often target mitochondrial dynamics as a part of their obligatory cellular reprogramming. The present study was undertaken to assess the status and regulation of mitochondrial dynamics during rotavirus infection. Distinct fragmentation of mitochondrial syncytia was observed during late hours of RV (SA11, Wa, A5-13) infection. RV nonstructural protein 4 (NSP4) was identified as the viral trigger for disrupted mitochondrial morphology. Severance of mitochondrial interconnections was found to be a dynamin-related protein 1 (Drp1)-dependent process resulting synergistically from augmented mitochondrial fission and attenuated mitochondrial fusion. Cyclin-dependent kinase 1 was subsequently identified as the cellular kinase responsible for fission-active Ser616 phosphorylation of Drp1. In addition to its positive role in mitochondrial fission, Drp1 also resulted in mitochondrial translocation of E3-ubiquitin ligase Parkin leading to degradation of mitochondrial fusion protein Mitofusin 1. Interestingly, RV-NSP4 was found to interact with and be involved in recruiting fission-active pool of Serine 616 phosphoDrp1 (Ser616 pDrp1) to mitochondria independent of accessory adaptors Mitochondrial fission factor and Fission protein 1 (Fis1). Inhibition of either Drp1 or Ser616 pDrp1 resulted in significant decrease in RV-NSP4-induced intrinsic apoptotic pathway. Overall, this study underscores an efficient strategy utilised by RV to couple apoptosis to mitochondrial fission facilitating dissemination of viral progeny.

show abstract

“…These proteins are resident OMM proteins and form rings and foci with a carboxy terminal domain and may be responsible for binding to inactive DRP1 dimers or inhibiting DRP1 GTPase activity [14,78,79]. MiD49 is a target of MARCH5 resulting in ubiquitylation and UPS dependent degradation [80].…”

Section: Outer Mitochondrial Membrane Fission and Fusionmentioning

confidence: 99%

“…MFF is an OMM localized protein required for mitochondrial fragmentation that may be required for recruitment of active DRP1 oligomers to the OMM or to activate DRP1 GTPase activity [13,15,78,79,81]. MFF is ubiquitylated by Parkin at a conserved lysine at position 251 after depolarization with mitochondrial uncouplers that results in loss of MFF protein.…”

Section: Outer Mitochondrial Membrane Fission and Fusionmentioning

confidence: 99%

Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein Turnover

Ali

McStay

2017

Preprint

View full text Add to dashboard Cite

The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as ATP synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space. Mitochondrial fission and fusion are performed by GTPases on the outer and inner mitochondrial membranes with the assistance of other mitochondrial proteins. Due to the essential nature of mitochondrial function for cellular homeostasis regulation of mitochondrial dynamics is under strict control. Some of the mechanisms used to regulate the function of these proteins are post-translational proteolysis and/or turnover and this review will discuss these mechanisms required for correct mitochondrial network organization. IntroductionMitochondria are the power houses of every nucleated cell, generating chemical energy in the form of adenosine triphosphate (ATP) by the oxidative phosphorylation (OXPHOS) system. Mitochondria are also important for the normal functioning of the cells as they regulate several crucial activities like differentiation, cell cycle, intracellular signaling and cell death [1]. Mitochondria are unique because of their autonomous DNA (mtDNA), which encodes for proteins required for ATP synthesis. Therefore maintenance of mtDNA is important for normal mitochondrial function and for the diversity of mitochondrial genome [2]. Mitochondria form elongated tubules that continually divide and fuse to form a complex, interconnected and highly dynamic network inside of cells. These dynamics processes not only regulate mitochondrial function but also mitochondrial shape, content exchange and mitochondrial communication with the cytoskeleton [3]. Due to the involvement of mitochondria in a large spectrum of cellular functions, these organelles play a key role in mediating cellular homeostasis. As a result a healthy population of mitochondria is critical for cell survival.

show abstract

Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission

Cited by 278 publications

References 63 publications

Structure, function, and regulation of mitofusin‐2 in health and disease

Structure, function, and regulation of mitofusin‐2 in health and disease

Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent mitochondrial fragmentation during infection

Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein Turnover

Contact Info

Product

Resources

About