Penninger JM et al. (2003) Nature Cell Biology "Mitochondria, AIF and caspases - rivaling for cell death execution."

Penninger JM, Kroemer G

[Nature Cell Biology, 2003]

In both the nematode Caenorhabditis elegans and mammals, two proteins released from the mitochondrion - apoptosis inducing factor (AIF) and endonuclease G - cooperate in executing programmed cell death. Although both factors can kill cells in a caspase-independent fashion, new studies indicate that their translocation from mitochondria depends, in part, on caspase activation. Together, these data raise new questions about the functional hierarchy between caspases, AIF and mitochondrial membrane

Joza N et al. (2009) Ann N Y Acad Sci "AIF: not just an apoptosis-inducing factor."

Kroemer G, Penninger JM, Modjtahedi N, Hangen E, Joza N, Pospisilik JA, Hanada T

[Ann N Y Acad Sci, 2009]

Since its discovery nearly a decade ago, apoptosis-inducing factor (AIF) has had anything but a staid and uneventful existence. AIF was originally described as a mitochondrial intermembrane protein that, after apoptosis induction, can translocate to the nucleus and trigger chromatin condensation and DNA fragmentation. Over the years, an AIF-mediated caspase-independent cell death pathway has been defined. Rather than functioning as a general component of the cell death machinery, AIF is required for specific cell death pathways, including lethal responses to excitotoxins such as N-methyl-D-aspartate and glutamate, the DNA-alkylating agent N-methyl-N'-nitro-N-nitroso-guanidine, hypoxia-ischemia, or growth factor deprivation. Also, important roles of AIF in mitochondrial metabolism and redox control, and more recently in obesity and diabetes, have been discovered. Much of our knowledge has come from studies of AIF orthologs in model organisms, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and mice, which have also highlighted the importance of AIF in animal physiology and human pathology. Here, we discuss the manifold nature of AIF in cell life and death, with particular emphasis of its roles in vivo.

Galluzzi L et al. (2017) EMBO J "Molecular definitions of autophagy and related processes."

Munz C, Boya P, Santambrogio L, Debnath J, Melendez A, Galluzzi L, Jaattela M, Ballabio A, Simon HU, Gewirtz DA, Bravo-San Pedro JM, Harper JW, Murphy LO, Tavernarakis N, Chu CT, Kroemer G, Deretic V, Dikic I, Fulda S, Martens S, Cuervo AM, Reggiori F, Green DR, Kimmelman AC, Levine B, Cecconi F, Penninger JM, Johansen T, Piacentini M, Codogno P, Choi AM, Madeo F, Lopez-Otin C, Simon AK, Juhasz G, Colombo MI, Fimia GM, Martinez J, Kraft C, Ryan KM, Yue Z, Hansen M, Zhong Q, Mizushima N, Simonsen A, Baehrecke EH, Ktistakis NT, Rubinsztein DC, Scorrano L, Tooze SA, Yoshimori T, Eskelinen EL, Yuan J, Kumar S

[EMBO J, 2017]

Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.